2FYJ

NMR Solution structure of calcium-loaded LRP double module

Summary for 2FYJ

• Entry DOI: 10.2210/pdb2fyj/pdb
• Related: 1LRE 2FYL
• NMR Information: BMRB: 5961
• Descriptor: Low-density lipoprotein receptor-related protein 1 (1 entity in total)
• Functional Keywords: double module, complement type repeat, calcium, beta-2 hairpin, loop-structures, protein binding
• 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: 8944.62

Authors

Jensen, G.A.,Andersen, O.M.,Bonvin, A.M.,Bjerrum-Bohr, I.,Etzerodt, M.,O'shea, C.,Poulsen, F.M.,Kragelund, B.B. (deposition date: 2006-02-08, release date: 2006-10-10, Last modification date: 2024-11-20)

Primary citation

Jensen, G.A.,Andersen, O.M.,Bonvin, A.M.,Bjerrum-Bohr, I.,Etzerodt, M.,O'shea, C.,Poulsen, F.M.,Kragelund, B.B.
Binding Site Structure of One LRP-RAP Complex:Implications for a Common Ligand-Receptor Binding Motif.
J.Mol.Biol., 362:700-716, 2006

PubMed Abstract: The low-density lipoprotein receptor-related protein (LRP) interacts with more than 30 ligands of different sizes and structures that can all be replaced by the receptor-associated protein (RAP). The double module of complement type repeats, CR56, of LRP binds many ligands including all three domains of RAP and alpha2-macroglobulin, which promotes the catabolism of the Abeta-peptide implicated in Alzheimer's disease. To understand the receptor-ligand cross-talk, the NMR structure of CR56 has been solved and ligand binding experiments with RAP domain 1 (RAPd1) have been performed. From chemical shift perturbations of both binding partners upon complex formation, a HADDOCK model of the complex between CR56 and RAPd1 has been obtained. The binding residues are similar to a common binding motif suggested from alpha2-macroglobulin binding studies and provide evidence for an understanding of their mutual cross-competition pattern. The present structural results convey a simultaneous description of both binding partners of an LRP-ligand complex and open a route to a broader understanding of the binding specificity of the LRP receptor, which may involve a general four-residue receptor-ligand recognition motif common to all LRP ligands. The present result may be beneficial in the design of antagonists of ligand binding to the LDL receptor family, and especially of drugs for treatment of Alzheimer's disease.

PubMed: 16938309
DOI: 10.1016/j.jmb.2006.07.013

Experimental method

SOLUTION NMR