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ID 34810
file
creator
Nakano, Shogo
Sugihara, Mamoru
Yamada, Risato
Tate, Shin-ichi
subject
C-type lectin-like domain
Oxidized low density lipoprotein
Atherosclerosis
Receptor structure
Pattern recognition receptor
NDC
Chemistry
abstract
Lectin-like oxidized lipoprotein (OxLDL) receptor 1, LOX-1, is the major OxLDL receptor expressed on vascular endothelial cells. We have previously reported the ligand-recognition mode of LOX-1 based on the crystal structure of the ligand binding domain (C-type lectin-like domain, CTLD) and surface plasmon resonance analysis, which suggested that the functional significance of the CTLD dimer (the 'canonical' dimer) is to harbor the characteristic "basic spine" on its surface. In this study, we have identified the key inter-domain interactions in retaining the canonical CTLD dimer by X-ray structural analysis of the inactive mutant W150A CTLD. The canonical CTLD dimer forms through tight hydrophobic interactions, in which W150 engages in a lock-and-key manner and represents the main interaction. The loss of the Trp ring by mutation to Ala prevents the formation of the canonical dimer, as elucidated from docking calculations using the crystal structure of W150A CTLD. The results emphasize that the canonically formed CTLD dimer is essential for LOX-1 to bind to OxLDL, which supports our proposed view that the basic spine surface present in the correctly formed dimer plays a primal role in OxLDL recognition. This concept provides insight into the pathogenic pattern recognized by LOX-1 as a member of the pattern recognition receptors.
journal title
Biochimica et Biophysica Acta - Proteins and Proteomics
volume
Volume 1824
issue
Issue 5
start page
739
end page
749
date of issued
2012
publisher
Elsevier Science BV
issn
1570-9639
ncid
publisher doi
language
eng
nii type
Journal Article
HU type
Journal Articles
DCMI type
text
format
application/pdf
text version
author
rights
(c) 2012 Elsevier B.V. All rights reserved.
relation url
department
Graduate School of Science