2FYL

Haddock model of the complex between double module of LRP, CR56, and first domain of receptor associated protein, RAP-d1.

2FYL の概要

• エントリーDOI: 10.2210/pdb2fyl/pdb
• 関連するPDBエントリー: 1LRE 2FYJ
• NMR情報: BMRB: 5961
• 分子名称: Alpha-2-macroglobulin receptor-associated protein, Low-density lipoprotein receptor-related protein 1, CALCIUM ION (3 entities in total)
• 機能のキーワード: complex, shift-mapping, haddock, interface, surface active protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Endoplasmic reticulum: P30533; 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
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 18560.78

構造登録者

Jensen, G.A.,Andersen, O.M.,Bonvin, A.M.,Bjerrum-Bohr, I.,Etzerodt, M.,O'shea, C.,Poulsen, F.M.,Kragelund, B.B. (登録日: 2006-02-08, 公開日: 2006-10-10, 最終更新日: 2024-10-30)

主引用文献

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

実験手法

SOLUTION NMR