PDBsum entry 1yxk

Lipid binding protein

PDB id: 1yxk

Contents

Protein chain

130 a.a. *

Waters ×52

* Residue conservation analysis

PDB id:

1yxk

Name:

Lipid binding protein

Title:

Crystal structure of human lectin-like oxidized low-density lipoprotein receptor 1 (lox-1) disulfide-linked dimer

Structure:

Oxidised low density lipoprotein (lectin-like) receptor 1. Chain: a, b. Fragment: ligand-binding domain. Synonym: lox-1. Engineered: yes

Source:

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

Resolution:

2.40Å R-factor: 0.218 R-free: 0.277

Authors:

I.Ohki,T.Ishigaki,T.Oyama,S.Matsunaga,Q.Xie,M.Ohnishi-Kameyama, T.Murata,D.Tsuchiya,S.Machida,K.Morikawa,S.Tate

Key ref:

I.Ohki et al. (2005). Crystal structure of human lectin-like, oxidized low-density lipoprotein receptor 1 ligand binding domain and its ligand recognition mode to OxLDL. Structure, 13, 905-917. PubMed id: 15939022 DOI: 10.1016/j.str.2005.03.016

Date:

22-Feb-05 Release date: 14-Jun-05

Protein chains

P78380  (OLR1_HUMAN) -  Oxidized low-density lipoprotein receptor 1 from Homo sapiens

Seq: 273 a.a.

Struc: 130 a.a.

DOI no: 10.1016/j.str.2005.03.016

Structure 13:905-917 (2005)

PubMed id: 15939022

Crystal structure of human lectin-like, oxidized low-density lipoprotein receptor 1 ligand binding domain and its ligand recognition mode to OxLDL.

I.Ohki, T.Ishigaki, T.Oyama, S.Matsunaga, Q.Xie, M.Ohnishi-Kameyama, T.Murata, D.Tsuchiya, S.Machida, K.Morikawa, S.Tate.

ABSTRACT

Lectin-like, oxidized low-density lipoprotein (LDL) receptor 1, LOX-1, is the major receptor for oxidized LDL (OxLDL) in endothelial cells. We have determined the crystal structure of the ligand binding domain of LOX-1, with a short stalk region connecting the domain to the membrane-spanning region, as a homodimer linked by an interchain disulfide bond. In vivo assays with LOX-1 mutants revealed that the "basic spine," consisting of linearly aligned arginine residues spanning over the dimer surface, is responsible for ligand binding. Single amino acid substitution in the dimer interface caused a severe reduction in LOX-1 binding activity, suggesting that the correct dimer arrangement is crucial for binding to OxLDL. Based on the LDL model structure, possible binding modes of LOX-1 to OxLDL are proposed.

Selected figure(s)

Figure 5.
Figure 5. The Empty Cavity in the Dimer Interface of LOX-1
(A) Empty cavity located at the dimer interface in the LOX-1 disulfide-lined dimer structure. The surrounding residues of the cavity are shown as bold lines.
(B) Possible effect of the W150A mutation on the basic spine structure on the LOX-1 ligand recognition surface. The W150A mutation may resize the empty cavity in the dimer interface, which subsequently disarranges the dimer, resulting in the disruption of the basic spine structure. The disrupted basic spine structure should lead to severe reduction of the binding ability to ligands.
(C) A plausible representation of the entire structure of LOX-1 at the cell surface, based on the crystal structure for CTLD and the model structure for the NECK. Modeling was performed by using the myosin heavy chain coiled-coil structure, which shows a high level of sequence homology to the NECK region.
(D) Scale comparison between the the OxLDL particle and LOX-1 dimer. The assembled structure of LOX-1 is drawn according to the results of cell biology studies that showed LOX-1 to exist as a hexamer on the cell surface (Xie et al., 2004). The diameter of OxLDL was estimated from cryoelectron microscopic observation of the LDL particle (Segrest et al., 2001). In this comparison, it is assumed that no significant structural alterations are induced by oxidation to the LDL particle.

The above figure is reprinted by permission from Cell Press: Structure (2005, 13, 905-917) copyright 2005.

Figure was selected by an automated process.