PMID- 10652313 OWN - NLM STAT- MEDLINE DCOM- 20000302 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 275 IP - 5 DP - 2000 Feb 4 TI - 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. PG - 3264-9 AB - 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. FAU - Dolmer, K AU - Dolmer K AD - Department of Biochemistry, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612-4316, USA. FAU - Huang, W AU - Huang W FAU - Gettins, P G AU - Gettins PG LA - eng SI - PDB/1 D21 GR - GM54414/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Low Density Lipoprotein Receptor-Related Protein-1) RN - 0 (Macrophage-1 Antigen) RN - 0 (Receptors, Immunologic) RN - 0 (alpha-Macroglobulins) SB - IM MH - Amino Acid Sequence MH - Binding Sites MH - Humans MH - Low Density Lipoprotein Receptor-Related Protein-1 MH - Macrophage-1 Antigen/chemistry MH - Magnetic Resonance Spectroscopy MH - Molecular Sequence Data MH - Receptors, Immunologic/*chemistry/metabolism MH - alpha-Macroglobulins/chemistry/metabolism EDAT- 2000/02/01 09:00 MHDA- 2000/03/04 09:00 CRDT- 2000/02/01 09:00 PHST- 2000/02/01 09:00 [pubmed] PHST- 2000/03/04 09:00 [medline] PHST- 2000/02/01 09:00 [entrez] AID - 10.1074/jbc.275.5.3264 [doi] AID - S0021-9258(18)30902-5 [pii] PST - ppublish SO - J Biol Chem. 2000 Feb 4;275(5):3264-9. doi: 10.1074/jbc.275.5.3264.