The Experts below are selected from a list of 1239 Experts worldwide ranked by ideXlab platform
Gottfried Otting - One of the best experts on this subject based on the ideXlab platform.
-
The Death-Domain Fold of the ASC PYRIN Domain, Presenting a Basis for PYRIN/PYRIN Recognition
Journal of molecular biology, 2003Co-Authors: Edvards Liepinsh, Raitis Barbals, Edgar Dahl, Anatoly Sharipo, Eike Staub, Gottfried OttingAbstract:The PYRIN Domain is a conserved sequence motif identified in more than 20 human proteins with putative functions in apoptotic and inflammatory signalling pathways. The three-dimensional structure of the PYRIN Domain from human ASC was determined by NMR spectroscopy. The structure determination reveals close structural similarity to Death Domains, Death effector Domains, and caspase activation and recruitment Domains, although the structural alignment with these other members of the Death-Domain Superfamily differs from previously predicted amino acid sequence alignments. Two highly positively and negatively charged surfaces in the PYRIN Domain of ASC result in a strong electrostatic dipole moment that is predicted to be present also in related PYRIN Domains. These results suggest that electrostatic interactions play an important role for the binding between PYRIN Domains. Consequently, the previously reported binding between the PYRIN Domains of ASC and ASC2/POP1 or between the zebrafish PYRIN Domains of zAsc and Caspy is proposed to involve interactions between helices 2 and 3 of one PYRIN Domain with helices 1 and 4 of the other PYRIN Domain, in analogy to previously reported homophilic interactions between caspase activation and recruitment Domains.
-
the Death Domain fold of the asc pyrin Domain presenting a basis for pyrin pyrin recognition
Journal of Molecular Biology, 2003Co-Authors: Edvards Liepinsh, Raitis Barbals, Edgar Dahl, Anatoly Sharipo, Eike Staub, Gottfried OttingAbstract:The PYRIN Domain is a conserved sequence motif identified in more than 20 human proteins with putative functions in apoptotic and inflammatory signalling pathways. The three-dimensional structure of the PYRIN Domain from human ASC was determined by NMR spectroscopy. The structure determination reveals close structural similarity to Death Domains, Death effector Domains, and caspase activation and recruitment Domains, although the structural alignment with these other members of the Death-Domain Superfamily differs from previously predicted amino acid sequence alignments. Two highly positively and negatively charged surfaces in the PYRIN Domain of ASC result in a strong electrostatic dipole moment that is predicted to be present also in related PYRIN Domains. These results suggest that electrostatic interactions play an important role for the binding between PYRIN Domains. Consequently, the previously reported binding between the PYRIN Domains of ASC and ASC2/POP1 or between the zebrafish PYRIN Domains of zAsc and Caspy is proposed to involve interactions between helices 2 and 3 of one PYRIN Domain with helices 1 and 4 of the other PYRIN Domain, in analogy to previously reported homophilic interactions between caspase activation and recruitment Domains.
Hyun Ho Park - One of the best experts on this subject based on the ideXlab platform.
-
structural transformation mediated dimerization of caspase recruitment Domain revealed by the crystal structure of card only protein in frog virus 3
Journal of Structural Biology, 2019Co-Authors: Chang Min Kim, Sunghark Kwon, Jaehee Jeong, Sung Hoon Lee, Yeongil Kim, Chang Sup Lee, Jun Hyuck Lee, Hyun Ho ParkAbstract:Abstract Caspase recruitment Domain (CARD)-only proteins (COPs), regulate apoptosis, inflammation, and innate immunity. They inhibit the assembly of NOD-like receptor complexes such as the inflammasome and NODosome, which are molecular complexes critical for caspase-1 activation. COPs are known to interact with either caspase-1 CARD or RIP2 CARD via a CARD-CARD interaction, and inhibit caspase-1 activation or further downstream signaling. In addition to the human COPs, Pseudo-ICE, INCA, and ICEBERG, several viruses also contain viral COPs that help them escape the host immune system. To elucidate the molecular mechanism of host immunity inhibition by viral COPs, we solved the structure of a viral COP for the first time. Our structure showed that viral COP forms a structural transformation-mediated dimer, which is unique and has not been reported in any structural study of a CARD Domain. Based on the current structure, and the previously solved structures of other Death Domain Superfamily members, we propose that structural transformation-mediated dimerization might be a new strategy for dimer assembly in the Death Domain Superfamily.
-
crystal structure of nalp3 protein pyrin Domain pyd and its implications in inflammasome assembly
Journal of Biological Chemistry, 2011Co-Authors: Ju Young Bae, Hyun Ho ParkAbstract:NALP3 inflammasome, composed of the three proteins NALP3, ASC, and Caspase-1, is a macromolecular complex responsible for the innate immune response against infection with bacterial and viral pathogens. Formation of the inflammasome can lead to the activation of inflammatory caspases, such as Caspase-1, which then activate pro-inflammatory cytokines by proteolytic cleavage. The assembly of the NALP3 inflammasome depends on the protein-interacting Domain known as the Death Domain Superfamily. NALP3 inflammasome is assembled via a pyrin Domain (PYD)/PYD interaction between ASC and NALP3 and a caspase recruitment Domain/caspase recruitment Domain interaction between ASC and Caspase-1. As a first step toward elucidating the molecular mechanisms of inflammatory caspase activation by formation of inflammasome, we report the crystal structure of the PYD from NALP3 at 1.7-A resolution. Although NALP3 PYD has the canonical six-helical bundle structural fold similar to other PYDs, the high resolution structure reveals the possible biologically important homodimeric interface and the dynamic properties of the fold. Comparison with other PYD structures shows both similarities and differences that may be functionally relevant. Structural and sequence analyses further implicate conserved surface residues in NALP3 PYD for ASC interaction and inflammasome assembly. The most interesting aspect of the structure was the unexpected disulfide bond between Cys-8 and Cys-108, which might be important for regulation of the activity of NALP3 by redox potential.
-
The Death Domain Superfamily in Intracellular Signaling of Apoptosis and Inflammation
Annual Review of Immunology, 2007Co-Authors: Hyun Ho Park, Yu Chih Lo, Jin Kuk Yang, Hao WuAbstract:The Death Domain (DD) Superfamily comprising the Death Domain (DD) subfamily, the Death effector Domain (DED) subfamily, the caspase recruitment Domain (CARD) subfamily, and the pyrin Domain (PYD) subfamily is one of the largest Domain superfamilies. By mediating homotypic interactions within each Domain subfamily, these proteins play important roles in the assembly and activation of apoptotic and inflammatory complexes. In this chapter, we review the molecular complexes assembled by these proteins, the structural and biochemical features of these Domains, and the molecular interactions mediated by them. By analyzing the potential molecular basis for the function of these Domains, we hope to provide a comprehensive understanding of the function, structure, interaction, and evolution of this important family of Domains.
Edvards Liepinsh - One of the best experts on this subject based on the ideXlab platform.
-
The Death-Domain Fold of the ASC PYRIN Domain, Presenting a Basis for PYRIN/PYRIN Recognition
Journal of molecular biology, 2003Co-Authors: Edvards Liepinsh, Raitis Barbals, Edgar Dahl, Anatoly Sharipo, Eike Staub, Gottfried OttingAbstract:The PYRIN Domain is a conserved sequence motif identified in more than 20 human proteins with putative functions in apoptotic and inflammatory signalling pathways. The three-dimensional structure of the PYRIN Domain from human ASC was determined by NMR spectroscopy. The structure determination reveals close structural similarity to Death Domains, Death effector Domains, and caspase activation and recruitment Domains, although the structural alignment with these other members of the Death-Domain Superfamily differs from previously predicted amino acid sequence alignments. Two highly positively and negatively charged surfaces in the PYRIN Domain of ASC result in a strong electrostatic dipole moment that is predicted to be present also in related PYRIN Domains. These results suggest that electrostatic interactions play an important role for the binding between PYRIN Domains. Consequently, the previously reported binding between the PYRIN Domains of ASC and ASC2/POP1 or between the zebrafish PYRIN Domains of zAsc and Caspy is proposed to involve interactions between helices 2 and 3 of one PYRIN Domain with helices 1 and 4 of the other PYRIN Domain, in analogy to previously reported homophilic interactions between caspase activation and recruitment Domains.
-
the Death Domain fold of the asc pyrin Domain presenting a basis for pyrin pyrin recognition
Journal of Molecular Biology, 2003Co-Authors: Edvards Liepinsh, Raitis Barbals, Edgar Dahl, Anatoly Sharipo, Eike Staub, Gottfried OttingAbstract:The PYRIN Domain is a conserved sequence motif identified in more than 20 human proteins with putative functions in apoptotic and inflammatory signalling pathways. The three-dimensional structure of the PYRIN Domain from human ASC was determined by NMR spectroscopy. The structure determination reveals close structural similarity to Death Domains, Death effector Domains, and caspase activation and recruitment Domains, although the structural alignment with these other members of the Death-Domain Superfamily differs from previously predicted amino acid sequence alignments. Two highly positively and negatively charged surfaces in the PYRIN Domain of ASC result in a strong electrostatic dipole moment that is predicted to be present also in related PYRIN Domains. These results suggest that electrostatic interactions play an important role for the binding between PYRIN Domains. Consequently, the previously reported binding between the PYRIN Domains of ASC and ASC2/POP1 or between the zebrafish PYRIN Domains of zAsc and Caspy is proposed to involve interactions between helices 2 and 3 of one PYRIN Domain with helices 1 and 4 of the other PYRIN Domain, in analogy to previously reported homophilic interactions between caspase activation and recruitment Domains.
Cengiz Yakicier - One of the best experts on this subject based on the ideXlab platform.
-
Research Communication Genetic Analysis of MEFV Gene Pyrin Domain in Patients With Behçet’s Disease
2016Co-Authors: Ahmet Dursun, Hatice Gul Durakbasi-dursun, Ayşe Gül Zamani, Zerrin Gülin Gulbahar, Recep Dursun, Cengiz YakicierAbstract:Objectives. Behçet’s disease (BD) is a systemic vasculitis with recurrent oral and genital ulcers and uveitis. MEFV gene, which is the main factor in familial Mediterranean fever (FMF), is also reported to be a susceptibility gene for BD. The pyrin Domain of MEFV gene is a member of Death-Domain Superfamily and has been proposed to regulate inflammatory signaling in myeloid cells. This study was designed to determine if mutations in pyrin Domain of MEFV gene are involved in BD. Methods. We analyzed the pyrin Domain of MEFV gene in 54 Turkish patients with BD by PCR-analysis and direct sequencing. Results. Neither deletion or insertion mutations nor point mutations in pyrin Domain were found in any patient. Conclusion. Although pyrin gene mutations have been reported in patients with BD, pyrin Domain is not mutated. However, alterations in other regions of MEFV gene and interaction between pyrin Domains are needed to be further investigated. Copyright © 2006 Ahmet Dursun et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
-
Genetic Analysis of MEFV Gene Pyrin Domain in Patients With Behçet's Disease
Mediators of Inflammation, 2006Co-Authors: Ahmet Dursun, Hatice Gul Durakbasi-dursun, Ayşe Gül Zamani, Zerrin Gülin Gulbahar, Recep Dursun, Cengiz YakicierAbstract:Objectives. Behcet's disease (BD) is a systemic vasculitis with recurrent oral and genital ulcers and uveitis. MEFV gene, which is the main factor in familial Mediterranean fever (FMF), is also reported to be a susceptibility gene for BD. The pyrin Domain of MEFV gene is a member of Death-Domain Superfamily and has been proposed to regulate inflammatory signaling in myeloid cells. This study was designed to determine if mutations in pyrin Domain of MEFV gene are involved in BD. Methods. We analyzed the pyrin Domain of MEFV gene in 54 Turkish patients with BD by PCR-analysis and direct sequencing. Results. Neither deletion or insertion mutations nor point mutations in pyrin Domain were found in any patient. Conclusion. Although pyrin gene mutations have been reported in patients with BD, pyrin Domain is not mutated. However, alterations in other regions of MEFV gene and interaction between pyrin Domains are needed to be further investigated.
Zhi Lin - One of the best experts on this subject based on the ideXlab platform.
-
structure of the c terminal Domain of tradd reveals a novel fold in the Death Domain Superfamily
Scientific Reports, 2017Co-Authors: Ning Zhang, Wensu Yuan, Jingsong Fan, Zhi LinAbstract:The TNFR1-associated Death Domain protein (TRADD) is an intracellular adaptor protein involved in various signaling pathways, such as antiapoptosis. Its C-terminal Death Domain (DD) is responsible for binding other DD-containing proteins including the p75 neurotrophin receptor (p75NTR). Here we present a solution structure of TRADD DD derived from high-resolution NMR spectroscopy. The TRADD DD comprises two super-secondary structures, an all-helix Greek key motif and a β-hairpin motif flanked by two α helices, which make it unique among all known DD structures. The β-hairpin motif is essential for TRADD DD to fold into a functional globular Domain. The highly-charged surface suggests a critical role of electrostatic interactions in TRADD DD-mediated signaling. This novel structure represents a new class within the DD Superfamily and provides a structural basis for studying homotypic DD interactions. NMR titration revealed a direct weak interaction between TRADD DD and p75NTR DD monomers. A binding site next to the p75NTR DD homodimerization interface indicates that TRADD DD recruitment to p75NTR requires separation of the p75NTR DD homodimer, explaining the mechanism of NGF-dependent activation of p75NTR-TRADD-mediated antiapoptotic pathway in breast cancer cell.
