PDBsum entry 2fyj

Protein binding

PDB id: 2fyj

Contents

Protein chain

82 a.a. *

* Residue conservation analysis

PDB id:

2fyj

Name:

Protein binding

Title:

Nmr solution structure of calcium-loaded lrp double module

Structure:

Low-density lipoprotein receptor-related protein 1. Chain: a. Synonym: lrp, alpha-2-macroglobulin receptor. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: lrp1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

NMR struc:

15 models

Authors:

G.A.Jensen,O.M.Andersen,A.M.Bonvin,I.Bjerrum-Bohr,M.Etzerodt, C.O'Shea,F.M.Poulsen,B.B.Kragelund

Key ref:

G.A.Jensen et al. (2006). Binding site structure of one LRP-RAP complex: implications for a common ligand-receptor binding motif. J Mol Biol, 362, 700-716. PubMed id: 16938309 DOI: 10.1016/j.jmb.2006.07.013

Date:

08-Feb-06 Release date: 10-Oct-06

Protein chain

Q07954  (LRP1_HUMAN) -  Prolow-density lipoprotein receptor-related protein 1 from Homo sapiens

Seq: 4544 a.a.

Struc: 82 a.a.

DOI no: 10.1016/j.jmb.2006.07.013

J Mol Biol 362:700-716 (2006)

PubMed id: 16938309

Binding site structure of one LRP-RAP complex: implications for a common ligand-receptor binding motif.

G.A.Jensen, O.M.Andersen, A.M.Bonvin, I.Bjerrum-Bohr, M.Etzerodt, H.C.Thøgersen, C.O'Shea, F.M.Poulsen, B.B.Kragelund.

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.

Selected figure(s)

Figure 4.
Figure 4. HADDOCK program model of the complex between RAPd1 and CR56 of LRP. (a) Backbone trace showing the three α-helices of RAPd1 and the two CR modules of CR56 with β-hairpins. (b) Hydrophobic interface with residues of Rapd1 and CR56 involved shown in van der Waals' surface representation in yellow and orange, respectively, and residues named accordingly. (c) The three networks of salt bridges between residues of RAPd1 and CR56. Network I is located below the hydrophobic cluster shown in (b) and network II at the rim of the interface.

Figure 7.
Figure 7. Suggested LRP recognition motif. (a) Schematic representation of the four residues D/E-K-W-Ψ interaction motif. Ψ is a hydrophobic residue or a residue with a significant non-polar part. (b)–(d) Views of the identified motifs in (b) LRP–RAP represented by the present HADDOCK model for CR56–RAPd1, (c) the structure of VLDLR in complex with the human rhinovirus (PDB accession code 1N7D) and (d) the low pH structure of LDL with interactions between LB5 and the β-propeller (PDB accession code 19VU).

The above figures are reprinted by permission from Elsevier: J Mol Biol (2006, 362, 700-716) copyright 2006.

Figures were selected by the author.