1d2l
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NMR SOLUTION STRUCTURE OF COMPLEMENT-LIKE REPEAT CR3 FROM THE LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN (LRP). EVIDENCE FOR SPECIFIC BINDING TO THE RECEPTOR BINDING DOMAIN OF HUMAN ALPHA-2 MACROGLOBULIN
OverviewOverview
We have used NMR methods to determine the structure of the calcium complex, of complement-like repeat 3 (CR3) from the low density lipoprotein, receptor-related protein (LRP) and to examine its specific interaction, with the receptor binding domain of human alpha(2)-macroglobulin. CR3 is, one of eight related repeats that constitute a major ligand binding region, of LRP. The structure is very similar in overall fold to homologous, complement-like repeat CR8 from LRP and complement-like repeats LB1, LB2, and LB5 from the low density lipoprotein receptor and contains a short, two-strand antiparallel beta-sheet, a one turn alpha-helix, and a high, affinity calcium site with coordination from four carboxyls and two, backbone carbonyls. The surface electrostatics and topography are, however, quite distinct from each of these other repeats. Two-dimensional, (1)H,(15)N-heteronuclear single quantum coherence spectra provide evidence, for a specific, though relatively weak (K(d) approximately 140 microM), interaction between CR3 and human alpha2-macroglobulin receptor binding, domain that involves a contiguous patch of surface residues in the central, region of CR3. This specific interaction is consistent with a mode of LRP, binding to ligands that uses contributions from more than one domain to, generate a wide array of different binding sites, each with overall high, affinity.
DiseaseDisease
Known diseases associated with this structure: Leigh syndrome, French-Canadian type OMIM:[607544], Urolithiasis, 2,8-dihydroxyadenine OMIM:[102600]
About this StructureAbout this Structure
1D2L is a Single protein structure of sequence from Homo sapiens with CA as ligand. Full crystallographic information is available from OCA.
ReferenceReference
NMR solution structure of complement-like repeat CR3 from the low density lipoprotein receptor-related protein. Evidence for specific binding to the receptor binding domain of human alpha(2)-macroglobulin., Dolmer K, Huang W, Gettins PG, J Biol Chem. 2000 Feb 4;275(5):3264-9. PMID:10652313
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