1D2L

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

Summary for 1D2L

• Entry DOI: 10.2210/pdb1d2l/pdb
• Related: 1CR8
• NMR Information: BMRB: 4514
• Descriptor: LIPOPROTEIN RECEPTOR RELATED PROTEIN, CALCIUM ION (2 entities in total)
• Functional Keywords: ligand binding, calcium binding, complement-like repeat, receptor, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Low-density lipoprotein receptor-related protein 1 85 kDa subunit: Cell membrane; Single-pass type I membrane protein. Low-density lipoprotein receptor-related protein 1 515 kDa subunit: Cell membrane; Peripheral membrane protein; Extracellular side. Low-density lipoprotein receptor-related protein 1 intracellular domain: Cytoplasm: Q07954
• Total number of polymer chains: 1
• Total formula weight: 4992.43

Authors

Dolmer, K.,Huang, W.,Gettins, P.G.W. (deposition date: 1999-09-24, release date: 2000-01-14, Last modification date: 2024-11-13)

Primary citation

Dolmer, K.,Huang, W.,Gettins, P.G.
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.
J.Biol.Chem., 275:3264-3269, 2000

PubMed Abstract: 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.

PubMed: 10652313
DOI: 10.1074/jbc.275.5.3264

Experimental method

SOLUTION NMR