The Experts below are selected from a list of 7986 Experts worldwide ranked by ideXlab platform

Javier Sancho - One of the best experts on this subject based on the ideXlab platform.

  • ldl receptor lipoprotein recognition endosomal weakening of apob and apoe binding to the Convex Face of the lr5 repeat
    FEBS Journal, 2014
    Co-Authors: Oscar Millet, Javier Sancho, Juan Martinezolivan, Xabier Ariasmoreno, Adrian Velazquezcampoy
    Abstract:

    The molecular mechanism of lipoprotein binding by the low-density lipoprotein (LDL) receptor (LDLR) is poorly understood, one reason being that structures of lipoprotein–receptor complexes are not available. LDLR uses calcium-binding repeats (LRs) to interact with apolipoprotein B and apolipoprotein E (ApoB and ApoE). We have used NMR and SPR to characterize the complexes formed by LR5 and three peptides encompassing the putative binding regions of ApoB (site A and site B) and ApoE. The three peptides bind at the hydrophilic Convex Face of LR5, forming complexes that are weakened at low [Ca2+] and low pH. Thus, endosomal conditions favour dissociation of LDLR/lipoprotein complexes regardless of whether active displacement of bound lipoproteins by the β-propeller in LDLR takes place. The multiple ApoE copies in β very low density lipoproteins (β-VLDLs), and the presence of two competent binding sites (A and B) in LDLs, suggest that LDLR chelates lipoproteins and enhances complex affinity by using more than one LR.

  • LDL receptor/lipoprotein recognition: endosomal weakening of ApoB and ApoE binding to the Convex Face of the LR5 repeat.
    The FEBS journal, 2014
    Co-Authors: Juan Martínez-oliván, Xabier Arias-moreno, Adrián Velázquez-campoy, Oscar Millet, Javier Sancho
    Abstract:

    The molecular mechanism of lipoprotein binding by the low-density lipoprotein (LDL) receptor (LDLR) is poorly understood, one reason being that structures of lipoprotein–receptor complexes are not available. LDLR uses calcium-binding repeats (LRs) to interact with apolipoprotein B and apolipoprotein E (ApoB and ApoE). We have used NMR and SPR to characterize the complexes formed by LR5 and three peptides encompassing the putative binding regions of ApoB (site A and site B) and ApoE. The three peptides bind at the hydrophilic Convex Face of LR5, forming complexes that are weakened at low [Ca2+] and low pH. Thus, endosomal conditions favour dissociation of LDLR/lipoprotein complexes regardless of whether active displacement of bound lipoproteins by the β-propeller in LDLR takes place. The multiple ApoE copies in β very low density lipoproteins (β-VLDLs), and the presence of two competent binding sites (A and B) in LDLs, suggest that LDLR chelates lipoproteins and enhances complex affinity by using more than one LR.

Ramnik J Xavier - One of the best experts on this subject based on the ideXlab platform.

  • leucine rich repeat lrr proteins integrators of pattern recognition and signaling in immunity
    Autophagy, 2011
    Co-Authors: Aylwin Ng, Ramnik J Xavier
    Abstract:

    The leucine-rich repeats (LRR)-containing domain is evolutionarily conserved in many proteins associated with innate immunity in plants, invertebrates and vertebrates. Serving as a first line of defense, the innate immune response is initiated through the sensing of pathogen-associated molecular patterns (PAMPs). In plants, NBS (nucleotide-binding site)-LRR proteins provide recognition of pathogen products of avirulence (AVR) genes. LRRs also promote interaction between LRR proteins as observed in receptor-coreceptor complexes. In mammals, toll-like receptors (TLRs) and NOD-like receptors (NLRs) through their LRR domain, sense molecular determinants from a structurally diverse set of bacterial, fungal, parasite and viral-derived components. In humans, at least 34 LRR proteins are implicated in diseases. Most LRR domains consist of 2–45 leucine-rich repeats, with each repeat about 20–30 residues long. Structurally, LRR domains adopt an arc or horseshoe shape, with the concave Face consisting of parallel β-strands and the Convex Face representing a more variable region of secondary structures including helices. Apart from the TLRs and NLRs, most of the 375 human LRR proteins remain uncharacterized functionally. We incorporated computational and functional analyses to facilitate multiFaceted insights into human LRR proteins and outline a few approaches here.

Marek Štancl - One of the best experts on this subject based on the ideXlab platform.

Aylwin Ng - One of the best experts on this subject based on the ideXlab platform.

  • leucine rich repeat lrr proteins integrators of pattern recognition and signaling in immunity
    Autophagy, 2011
    Co-Authors: Aylwin Ng, Ramnik J Xavier
    Abstract:

    The leucine-rich repeats (LRR)-containing domain is evolutionarily conserved in many proteins associated with innate immunity in plants, invertebrates and vertebrates. Serving as a first line of defense, the innate immune response is initiated through the sensing of pathogen-associated molecular patterns (PAMPs). In plants, NBS (nucleotide-binding site)-LRR proteins provide recognition of pathogen products of avirulence (AVR) genes. LRRs also promote interaction between LRR proteins as observed in receptor-coreceptor complexes. In mammals, toll-like receptors (TLRs) and NOD-like receptors (NLRs) through their LRR domain, sense molecular determinants from a structurally diverse set of bacterial, fungal, parasite and viral-derived components. In humans, at least 34 LRR proteins are implicated in diseases. Most LRR domains consist of 2–45 leucine-rich repeats, with each repeat about 20–30 residues long. Structurally, LRR domains adopt an arc or horseshoe shape, with the concave Face consisting of parallel β-strands and the Convex Face representing a more variable region of secondary structures including helices. Apart from the TLRs and NLRs, most of the 375 human LRR proteins remain uncharacterized functionally. We incorporated computational and functional analyses to facilitate multiFaceted insights into human LRR proteins and outline a few approaches here.

Juan Martinezolivan - One of the best experts on this subject based on the ideXlab platform.

  • ldl receptor lipoprotein recognition endosomal weakening of apob and apoe binding to the Convex Face of the lr5 repeat
    FEBS Journal, 2014
    Co-Authors: Oscar Millet, Javier Sancho, Juan Martinezolivan, Xabier Ariasmoreno, Adrian Velazquezcampoy
    Abstract:

    The molecular mechanism of lipoprotein binding by the low-density lipoprotein (LDL) receptor (LDLR) is poorly understood, one reason being that structures of lipoprotein–receptor complexes are not available. LDLR uses calcium-binding repeats (LRs) to interact with apolipoprotein B and apolipoprotein E (ApoB and ApoE). We have used NMR and SPR to characterize the complexes formed by LR5 and three peptides encompassing the putative binding regions of ApoB (site A and site B) and ApoE. The three peptides bind at the hydrophilic Convex Face of LR5, forming complexes that are weakened at low [Ca2+] and low pH. Thus, endosomal conditions favour dissociation of LDLR/lipoprotein complexes regardless of whether active displacement of bound lipoproteins by the β-propeller in LDLR takes place. The multiple ApoE copies in β very low density lipoproteins (β-VLDLs), and the presence of two competent binding sites (A and B) in LDLs, suggest that LDLR chelates lipoproteins and enhances complex affinity by using more than one LR.