L27 Domain

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Jiafu Long - One of the best experts on this subject based on the ideXlab platform.

  • structure of an L27 Domain heterotrimer from cell polarity complex patj pals1 mals2 reveals mutually independent L27 Domain assembly mode
    Journal of Biological Chemistry, 2012
    Co-Authors: Jinxiu Zhang, Xue Yang, Xingqiao Xie, Hao Zhou, Zheng Wang, Yuequan Shen, Jiafu Long
    Abstract:

    The assembly of supramolecular complexes in multiDomain scaffold proteins is crucial for the control of cell polarity. The scaffold protein of protein associated with Lin-7 1 (Pals1) forms a complex with two other scaffold proteins, Pals-associated tight junction protein (Patj) and mammalian homolog-2 of Lin-7 (Mals2), through its tandem Lin-2 and Lin-7 (L27) Domains to regulate apical-basal polarity. Here, we report the crystal structure of a 4-L27 Domain-containing heterotrimer derived from the tripartite complex Patj/Pals1/Mals2. The heterotrimer consists of two cognate pairs of heterodimeric L27 Domains with similar conformations. Structural analysis and biochemical data further show that the dimers assemble mutually independently. Additionally, such mutually independent assembly of the two heterodimers can be observed in another tripartite complex, Disks large homolog 1 (DLG1)/calcium-calmodulin-dependent serine protein kinase (CASK)/Mals2. Our results reveal a novel mechanism for tandem L27 Domain-mediated, supramolecular complex assembly with a mutually independent mode.

  • Structure of an L27 Domain Heterotrimer from Cell Polarity Complex Patj/Pals1/Mals2 Reveals Mutually Independent L27 Domain Assembly Mode
    The Journal of biological chemistry, 2012
    Co-Authors: Jinxiu Zhang, Xue Yang, Xingqiao Xie, Hao Zhou, Zheng Wang, Yuequan Shen, Jiafu Long
    Abstract:

    The assembly of supramolecular complexes in multiDomain scaffold proteins is crucial for the control of cell polarity. The scaffold protein of protein associated with Lin-7 1 (Pals1) forms a complex with two other scaffold proteins, Pals-associated tight junction protein (Patj) and mammalian homolog-2 of Lin-7 (Mals2), through its tandem Lin-2 and Lin-7 (L27) Domains to regulate apical-basal polarity. Here, we report the crystal structure of a 4-L27 Domain-containing heterotrimer derived from the tripartite complex Patj/Pals1/Mals2. The heterotrimer consists of two cognate pairs of heterodimeric L27 Domains with similar conformations. Structural analysis and biochemical data further show that the dimers assemble mutually independently. Additionally, such mutually independent assembly of the two heterodimers can be observed in another tripartite complex, Disks large homolog 1 (DLG1)/calcium-calmodulin-dependent serine protein kinase (CASK)/Mals2. Our results reveal a novel mechanism for tandem L27 Domain-mediated, supramolecular complex assembly with a mutually independent mode.

  • Structural basis for tandem L27 Domain-mediated polymerization
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010
    Co-Authors: Xue Yang, Xingqiao Xie, Liu Chen, Hao Zhou, Zheng Wang, Weijing Zhao, Ran Tian, Rongguang Zhang, Changlin Tian, Jiafu Long
    Abstract:

    The establishment of epithelial cell polarity requires the assembly of multiprotein complexes and is crucial during epithelial morphogenesis. Three scaffolding proteins, Dlg1, MPP7, and Mals3, can be assembled to form a complex that functions in the establishment and maintenance of apicobasal polarity in epithelial tissues through their L27 Domains. Here we report the crystal structure of a 4-L27-Domain complex derived from the human tripartite complex Dlg1-MPP7-Mals3 in combination with paramagnetic relaxation enhancement measurements. The heterotrimer consists of 2 pairs of heterodimeric L27 Domains. These 2 dimers are asymmetric due to the large difference between the N- and C-terminal tandem L27 Domain of MPP7. Structural analysis combined with biochemical experiments further reveals that the loop αA-αB and helix αB of the C-terminal L27 Domain of MPP7 play a critical role in assembling the entire tripartite complex, suggesting a synergistic tandem L27-mediated assembling event.—Yang, X., Xie, X., Che...

  • a unified assembly mode revealed by the structures of tetrameric L27 Domain complexes formed by mlin 2 mlin 7 and patj pals1 scaffold proteins
    Proceedings of the National Academy of Sciences of the United States of America, 2005
    Co-Authors: Wei Feng, Jiafu Long, Mingjie Zhang
    Abstract:

    Initially identified in Caenorhabditis elegans Lin-2 and Lin-7, L27 Domain is a proteinprotein interaction Domain capable of organizing scaffold proteins into supramolecular assemblies by formation of heteromeric L27 Domain complexes. L27 Domain-mediated protein assemblies have been shown to play essential roles in cellular processes including asymmetric cell division, establishment and maintenance of cell polarity, and clustering of receptors and ion channels. The structural basis of L27 Domain heteromeric complex assembly is controversial. We determined the high-resolution solution structure of the prototype L27 Domain complex formed by mLin-2 and mLin-7 as well as the solution structure of the L27 Domain complex formed by Patj and Pals1. The structures suggest that a tetrameric structure composed of two units of heterodimer is a general assembly mode for cognate pairs of L27 Domains. Structural analysis of the L27 Domain complex structures further showed that the central four-helix bundles mediating tetramer assembly are highly distinct between different pairs of L27 Domain complexes. Biochemical studies revealed that the C-terminal α-helix responsible for the formation of the central helix bundle is a critical specificity determinant for each L27 Domain in choosing its binding partner. Our results provide a unified picture for L27 Domain-mediated proteinprotein interactions.

  • A unified assembly mode revealed by the structures of tetrameric L27 Domain complexes formed by mLin-2/mLin-7 and Patj/Pals1 scaffold proteins.
    Proceedings of the National Academy of Sciences of the United States of America, 2005
    Co-Authors: Wei Feng, Jiafu Long, Mingjie Zhang
    Abstract:

    Initially identified in Caenorhabditis elegans Lin-2 and Lin-7, L27 Domain is a proteinprotein interaction Domain capable of organizing scaffold proteins into supramolecular assemblies by formation of heteromeric L27 Domain complexes. L27 Domain-mediated protein assemblies have been shown to play essential roles in cellular processes including asymmetric cell division, establishment and maintenance of cell polarity, and clustering of receptors and ion channels. The structural basis of L27 Domain heteromeric complex assembly is controversial. We determined the high-resolution solution structure of the prototype L27 Domain complex formed by mLin-2 and mLin-7 as well as the solution structure of the L27 Domain complex formed by Patj and Pals1. The structures suggest that a tetrameric structure composed of two units of heterodimer is a general assembly mode for cognate pairs of L27 Domains. Structural analysis of the L27 Domain complex structures further showed that the central four-helix bundles mediating tetramer assembly are highly distinct between different pairs of L27 Domain complexes. Biochemical studies revealed that the C-terminal α-helix responsible for the formation of the central helix bundle is a critical specificity determinant for each L27 Domain in choosing its binding partner. Our results provide a unified picture for L27 Domain-mediated proteinprotein interactions.

Jimena Sierralta - One of the best experts on this subject based on the ideXlab platform.

  • Presynaptic DLG regulates synaptic function through the localization of voltage-activated Ca^2+ Channels
    Scientific Reports, 2016
    Co-Authors: César Astorga, Ramón A. Jorquera, Mauricio Ramírez, Andrés Kohler, Estefanía López, Ricardo Delgado, Alex Córdova, Patricio Olguín, Jimena Sierralta
    Abstract:

    The DLG-MAGUK subfamily of proteins plays a role on the recycling and clustering of glutamate receptors (GLUR) at the postsynaptic density. discs-large1 ( dlg ) is the only DLG-MAGUK gene in Drosophila and originates two main products, DLGA and DLGS97 which differ by the presence of an L27 Domain. Combining electrophysiology, immunostaining and genetic manipulation at the pre and postsynaptic compartments we study the DLG contribution to the basal synaptic-function at the Drosophila larval neuromuscular junction. Our results reveal a specific function of DLGS97 in the regulation of the size of GLUR fields and their subunit composition. Strikingly the absence of any of DLG proteins at the presynaptic terminal disrupts the clustering and localization of the calcium channel DmCa1A subunit (Cacophony), decreases the action potential-evoked release probability and alters short-term plasticity. Our results show for the first time a crucial role of DLG proteins in the presynaptic function in vivo .

  • Presynaptic DLG regulates synaptic function through the localization of voltage-activated Ca2+ Channels
    Scientific reports, 2016
    Co-Authors: César Astorga, Ramón A. Jorquera, Mauricio Ramírez, Andrés Kohler, Estefanía López, Ricardo Delgado, Alex Córdova, Patricio Olguín, Jimena Sierralta
    Abstract:

    The DLG-MAGUK subfamily of proteins plays a role on the recycling and clustering of glutamate receptors (GLUR) at the postsynaptic density. discs-large1 (dlg) is the only DLG-MAGUK gene in Drosophila and originates two main products, DLGA and DLGS97 which differ by the presence of an L27 Domain. Combining electrophysiology, immunostaining and genetic manipulation at the pre and postsynaptic compartments we study the DLG contribution to the basal synaptic-function at the Drosophila larval neuromuscular junction. Our results reveal a specific function of DLGS97 in the regulation of the size of GLUR fields and their subunit composition. Strikingly the absence of any of DLG proteins at the presynaptic terminal disrupts the clustering and localization of the calcium channel DmCa1A subunit (Cacophony), decreases the action potential-evoked release probability and alters short-term plasticity. Our results show for the first time a crucial role of DLG proteins in the presynaptic function in vivo.

  • A perisynaptic ménage à trois between Dlg, DLin-7, and Metro controls proper organization of Drosophila synaptic junctions.
    The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010
    Co-Authors: André Bachmann, Elisabeth Knust, Jimena Sierralta, Oliver Kobler, Robert J. Kittel, Carolin Wichmann, Stephan J. Sigrist, Eckart D. Gundelfinger, Ulrich Thomas
    Abstract:

    Structural plasticity of synaptic junctions is a prerequisite to achieve and modulate connectivity within nervous systems, e.g., during learning and memory formation. It demands adequate backup systems that allow remodeling while retaining sufficient stability to prevent unwanted synaptic disintegration. The strength of submembranous scaffold complexes, which are fundamental to the architecture of synaptic junctions, likely constitutes a crucial determinant of synaptic stability. Postsynaptic density protein-95 (PSD-95)/ Discs-large (Dlg)-like membrane-associated guanylate kinases (DLG-MAGUKs) are principal scaffold proteins at both vertebrate and invertebrate synapses. At Drosophila larval glutamatergic neuromuscular junctions (NMJs) DlgA and DlgS97 exert pleiotropic functions, probably reflecting a few known and a number of yet-unknown binding partners. In this study we have identified Metro, a novel p55/MPP-like Drosophila MAGUK as a major binding partner of perisynaptic DlgS97 at larval NMJs. Based on homotypic LIN-2,-7 (L27) Domain interactions, Metro stabilizes junctional DlgS97 in a complex with the highly conserved adaptor protein DLin-7. In a remarkably interdependent manner, Metro and DLin-7 act downstream of DlgS97 to control NMJ expansion and proper establishment of synaptic boutons. Using quantitative 3D-imaging we further demonstrate that the complex controls the size of postsynaptic glutamate receptor fields. Our findings accentuate the importance of perisynaptic scaffold complexes for synaptic stabilization and organization.

  • Temporal and spatial expression of Drosophila DLGS97 during neural development.
    Gene expression patterns : GEP, 2008
    Co-Authors: Valeria Albornoz, Patricio Olguín, Carolina Mendoza-topaz, Carlos Oliva, Judith A. Tello, Jimena Sierralta
    Abstract:

    The products of the Drosophila discs-large (dlg) gene are members of the MAGUK family of proteins, a group of proteins involved in localization, transport and recycling of receptors and channels in cell junctions, including the synapse. In vertebrates, four genes with multiple splice variants homologous to dlg are described. dlg originates two main proteins, DLGA, similar to the vertebrate neuronal protein PSD95, and DLGS97, similar to the vertebrate neuronal and epithelial protein SAP97. DLGA is expressed in epithelia, neural tissue and muscle. DLGS97 is expressed in neural tissue and muscle but not in epithelia. The distinctive difference between them is the presence in DLGS97 of an L27 Domain. The differential expression between these variants makes the study of DLGS97 of key relevance to understand the in vivo role of synaptic MAGUKs in neurons. Here we present the temporal and spatial expression pattern of DLGS97 during embryonic and larval nervous system development, during eye development and in adult brain. Our results show that DLGS97 is expressed zygotically, in neurons in the embryo, larvae and adult, and is absent at all stages in glial cells. During eye development DLGS97 starts to be expressed in photoreceptor cells at early stages of differentiation and localizes basal to the basolateral junctions. In the brain, DLGS97 is expressed in the mushroom bodies and optic lobes at larval and adult stages; and in the antennal lobe in the adult stage. In addition we show that both, dlgS97 and dlgA transcripts, express during development multiple splice variants with differences in the use of exons in two sites.

Wendell A. Lim - One of the best experts on this subject based on the ideXlab platform.

  • A general model for preferential hetero-oligomerization of LIN-2/7 Domains : Mechanism underlying directed assembly of supramolecular signaling complexes
    The Journal of biological chemistry, 2005
    Co-Authors: Keiko Y. Petrosky, Frank Löhr, Volker Dötsch, Wendell A. Lim
    Abstract:

    LIN-2/7 (L27) Domains are protein interaction modules that preferentially hetero-oligomerize, a property critical for their function in directing specific assembly of supramolecular signaling complexes at synapses and other polarized cell-cell junctions. We have solved the solution structure of the heterodimer composed of the L27 Domains from LIN-2 and LIN-7. Comparison of this structure with other L27 Domain structures has allowed us to formulate a general model for why most L27 Domains form an obligate heterodimer complex. L27 Domains can be divided in two types (A and B), with each heterodimer comprising an A/B pair. We have identified two keystone positions that play a central role in discrimination. The residues at these positions are energetically acceptable in the context of an A/B heterodimer, but would lead to packing defects or electrostatic repulsion in the context of A/A and B/B homodimers. As predicted by the model, mutations of keystone residues stabilize normally strongly disfavored homodimers. Thus, L27 Domains are specifically optimized to avoid homodimeric interactions.

  • A General Model for Preferential Hetero-oligomerization of LIN-2/7 Domains MECHANISMUNDERLYINGDIRECTEDASSEMBLYOFSUPRAMOLECULAR
    2005
    Co-Authors: Keiko Y. Petrosky, Wendell A. Lim
    Abstract:

    LIN-2/7 (L27) Domains are protein interaction modules that preferentially hetero-oligomerize, a property critical for their function in directing specific assembly of supramolecular signaling complexes at synapses and other polarized cell-cell junctions. We have solved the solution structure of the heterodimer composed of the L27 Domains from LIN-2 and LIN-7. Comparison of this structure with other L27 Domain structures has allowed us to formulate a general model for why most L27 Domains form an obligate heterodimer complex. L27 Domains can be divided in two types (A and B), with each heterodimer comprising an A/B pair. We have identified two keystone positions that play a central role in discrimination. The residues at these positions are energetically acceptable in the context of an A/B heterodimer, but would lead to packing defects or electrostatic repulsion in the context of A/A and B/B homodimers. As predicted by the model, mutations of keystone residues stabilize normally strongly disfavored homodimers. Thus, L27 Domains are specifically optimized to avoid homodimeric interactions.

  • Coordinated Folding and Association of the LIN-2, -7 (L27) Domain: AN OBLIGATE HETERODIMERIZATION MODULE INVOLVED IN ASSEMBLY OF SIGNALING AND CELL POLARITY COMPLEXES
    The Journal of biological chemistry, 2002
    Co-Authors: Baruch Z. Harris, Shivkumar Venkatasubrahmanyam, Wendell A. Lim
    Abstract:

    LIN-2, -7 (L27) homology Domains are putative protein-protein interaction modules found in several scaffold proteins involved in the assembly of polarized cell-signaling structures. These specific interaction pairs are well conserved across metazoan species, from worms to man. We have expressed and purified L27 Domains from multiple species and find that certain Domains from proteins such as Caenorhabditis elegans LIN-2 and LIN-7 can specifically heterodimerize. Biophysical analysis of interacting L27 Domains demonstrates that the Domains interact with a 1:1 stoichiometry. Circular dichroism studies reveal that the Domains appear to function as an obligate heterodimer; individually the Domains are largely unfolded, but when associated they show a significant increase in helicity, as well as a cooperative unfolding transition. These novel obligate interacting pairs are likely to play a key role in regulating the organization of signaling proteins at polarized cell structures.

Ben Margolis - One of the best experts on this subject based on the ideXlab platform.

  • Mammalian Lin-7 Stabilizes Polarity Protein Complexes
    The Journal of biological chemistry, 2006
    Co-Authors: Samuel W Straight, Jay N. Pieczynski, Eileen L. Whiteman, Chia Jen Liu, Ben Margolis
    Abstract:

    Mammalian Lin-7 forms a complex with several proteins, including PALS1, that have a role in polarity determination in epithelial cells. In this study we have found that loss of Lin-7 protein from the polarized epithelial cell line Madin-Darby canine kidney II by small hairpin RNA results in defects in tight junction formation as indicated by lowered transepithelial electrical resistance and mislocalization of the tight junction protein ZO-1 after calcium switch. The knock down of Lin-7 also resulted in the loss of expression of several Lin-7 binding partners, including PALS1 and the polarity protein PATJ. The effects of Lin-7 knock down were rescued by the exogenous expression of murine Lin-7 constructs that contained the L27 Domain, but not the PDZ Domain alone. Furthermore, exogenously expressed PALS1, but not other Lin-7 binding partners, also rescued the effects of Lin-7 knock down, including the restoration of PATJ protein in rescued cell lines. Finally, the effects of Lin-7 knock down appeared to be due to instability of PALS1 protein in the absence of Lin-7, as indicated by an increased rate of PALS1 protein degradation. Taken together, these results indicate that Lin-7 functions in tight junction formation by stabilizing its membrane-associated guanylate kinase binding partner PALS1.

  • structural basis for L27 Domain mediated assembly of signaling and cell polarity complexes
    The EMBO Journal, 2004
    Co-Authors: David Karnak, Borries Demeler, Ben Margolis, Arnon Lavie
    Abstract:

    L27 is a protein-binding Domain that can assemble essential proteins for signaling and cell polarity into complexes by interacting in a heterodimeric manner. One of these protein complexes is the PATJ/PALS1/Crumbs tripartite complex, which is crucial for the establishment and maintenance of cell polarity. To reveal the structural basis underlining the obligate heterodimerization, we have determined the crystal structure of the PALS1-L27N/PATJ-L27 heterodimer complex. Each L27 Domain is composed of three helices. The two L27 Domains heterodimerize by building a compact structure consisting of a four-helix bundle formed by the first two helices of each L27 Domain and one coiled-coil formed by the third helix of each Domain. The large hydrophobic packing interactions contributed by all the helices of both L27 Domains predominantly drive the heterodimer formation, which is likely to be a general feature of L27 Domains. Combined with mutational studies, we can begin to understand the structural basis for the specificity of L27 binding pairs. Our results provide unique insights into L27 Domain heterodimer complex, which is critical for cell polarization.

  • Structural basis for L27 Domain‐mediated assembly of signaling and cell polarity complexes
    The EMBO journal, 2004
    Co-Authors: David Karnak, Borries Demeler, Ben Margolis, Arnon Lavie
    Abstract:

    L27 is a protein-binding Domain that can assemble essential proteins for signaling and cell polarity into complexes by interacting in a heterodimeric manner. One of these protein complexes is the PATJ/PALS1/Crumbs tripartite complex, which is crucial for the establishment and maintenance of cell polarity. To reveal the structural basis underlining the obligate heterodimerization, we have determined the crystal structure of the PALS1-L27N/PATJ-L27 heterodimer complex. Each L27 Domain is composed of three helices. The two L27 Domains heterodimerize by building a compact structure consisting of a four-helix bundle formed by the first two helices of each L27 Domain and one coiled-coil formed by the third helix of each Domain. The large hydrophobic packing interactions contributed by all the helices of both L27 Domains predominantly drive the heterodimer formation, which is likely to be a general feature of L27 Domains. Combined with mutational studies, we can begin to understand the structural basis for the specificity of L27 binding pairs. Our results provide unique insights into L27 Domain heterodimer complex, which is critical for cell polarization.

  • a novel and conserved protein protein interaction Domain of mammalian lin 2 cask binds and recruits sap97 to the lateral surface of epithelia
    Molecular and Cellular Biology, 2002
    Co-Authors: Seonok Lee, Shuling Fan, Olya Makarova, Samuel W Straight, Ben Margolis
    Abstract:

    Mammalian Lin-2 (mLin-2)/CASK is a membrane-associated guanylate kinase (MAGUK) and contains multiDomain modules that mediate protein-protein interactions important for the establishment and maintenance of neuronal and epithelial cell polarization. The importance of mLin-2/CASK in mammalian development is demonstrated by the fact that mutations in mLin-2/CASK or SAP97, another MAGUK protein, lead to cleft palate in mice. We recently identified a new protein-protein interaction Domain, called the L27 Domain, which is present twice in mLin-2/CASK. In this report, we further define the binding of the L27C Domain of mLin-2/CASK to the L27 Domain of mLin-7 and identify the binding partner for L27N of mLin-2/CASK. Biochemical analysis reveals that this L27N Domain binds to the N terminus of SAP97, a region that was previously reported to be essential for the lateral membrane recruitment of SAP97 in epithelia. Our colocalization studies, using dominant-negative mLin-2/CASK, show that the association with mLin-2/CASK is crucial for lateral localization of SAP97 in MDCK cells. We also report the identification of a novel isoform of Discs Large, a Drosophila melanogaster orthologue of SAP97, which contains a region highly related to the SAP97 N terminus and which binds Camguk, a Drosophila orthologue of mLin-2/CASK. Our data identify evolutionarily conserved protein-protein interaction Domains that link mLin-2/CASK to SAP97 and account for their common phenotype when mutated in mice.

Mingjie Zhang - One of the best experts on this subject based on the ideXlab platform.

  • a unified assembly mode revealed by the structures of tetrameric L27 Domain complexes formed by mlin 2 mlin 7 and patj pals1 scaffold proteins
    Proceedings of the National Academy of Sciences of the United States of America, 2005
    Co-Authors: Wei Feng, Jiafu Long, Mingjie Zhang
    Abstract:

    Initially identified in Caenorhabditis elegans Lin-2 and Lin-7, L27 Domain is a proteinprotein interaction Domain capable of organizing scaffold proteins into supramolecular assemblies by formation of heteromeric L27 Domain complexes. L27 Domain-mediated protein assemblies have been shown to play essential roles in cellular processes including asymmetric cell division, establishment and maintenance of cell polarity, and clustering of receptors and ion channels. The structural basis of L27 Domain heteromeric complex assembly is controversial. We determined the high-resolution solution structure of the prototype L27 Domain complex formed by mLin-2 and mLin-7 as well as the solution structure of the L27 Domain complex formed by Patj and Pals1. The structures suggest that a tetrameric structure composed of two units of heterodimer is a general assembly mode for cognate pairs of L27 Domains. Structural analysis of the L27 Domain complex structures further showed that the central four-helix bundles mediating tetramer assembly are highly distinct between different pairs of L27 Domain complexes. Biochemical studies revealed that the C-terminal α-helix responsible for the formation of the central helix bundle is a critical specificity determinant for each L27 Domain in choosing its binding partner. Our results provide a unified picture for L27 Domain-mediated proteinprotein interactions.

  • A unified assembly mode revealed by the structures of tetrameric L27 Domain complexes formed by mLin-2/mLin-7 and Patj/Pals1 scaffold proteins.
    Proceedings of the National Academy of Sciences of the United States of America, 2005
    Co-Authors: Wei Feng, Jiafu Long, Mingjie Zhang
    Abstract:

    Initially identified in Caenorhabditis elegans Lin-2 and Lin-7, L27 Domain is a proteinprotein interaction Domain capable of organizing scaffold proteins into supramolecular assemblies by formation of heteromeric L27 Domain complexes. L27 Domain-mediated protein assemblies have been shown to play essential roles in cellular processes including asymmetric cell division, establishment and maintenance of cell polarity, and clustering of receptors and ion channels. The structural basis of L27 Domain heteromeric complex assembly is controversial. We determined the high-resolution solution structure of the prototype L27 Domain complex formed by mLin-2 and mLin-7 as well as the solution structure of the L27 Domain complex formed by Patj and Pals1. The structures suggest that a tetrameric structure composed of two units of heterodimer is a general assembly mode for cognate pairs of L27 Domains. Structural analysis of the L27 Domain complex structures further showed that the central four-helix bundles mediating tetramer assembly are highly distinct between different pairs of L27 Domain complexes. Biochemical studies revealed that the C-terminal α-helix responsible for the formation of the central helix bundle is a critical specificity determinant for each L27 Domain in choosing its binding partner. Our results provide a unified picture for L27 Domain-mediated proteinprotein interactions.

  • The tetrameric L27 Domain complex as an organization platform for supramolecular assemblies.
    Nature structural & molecular biology, 2004
    Co-Authors: Wei Feng, Jiafu Long, Jing-song Fan, Tetsuya Suetake, Mingjie Zhang
    Abstract:

    L27 Domain, initially identified in the Caenorhabditis elegans Lin-2 and Lin-7 proteins, is a protein interaction module that exists in a large family of scaffold proteins. The Domain can function as an organization center of large protein assemblies required for establishment and maintenance of cell polarity. We have solved the high-resolution NMR structure of a tetrameric complex of L27 Domains containing two SAP97–mLin-2 L27 Domain heterodimers. Each L27 Domain contains three � -helices. The first two helices of each Domain are packed together to form a four-helical bundle in the heterodimer. The third helix of each L27 Domain forms another four-helical bundle that assembles the two heterodimers into a tetramer. The structure of the complex provides a mechanistic explanation for L27 Domain–mediated polymerization of scaffold proteins, a process that is crucial for the assembly of supramolecular complexes in asymmetric cells.