このエントリーをはてなブックマークに追加
ID 34810
本文ファイル
著者
Nakano, Shogo
Sugihara, Mamoru
Yamada, Risato
Tate, Shin-ichi
キーワード
C-type lectin-like domain
Oxidized low density lipoprotein
Atherosclerosis
Receptor structure
Pattern recognition receptor
NDC
化学
抄録(英)
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.
掲載誌名
Biochimica et Biophysica Acta - Proteins and Proteomics
1824巻
5号
開始ページ
739
終了ページ
749
出版年月日
2012
出版者
Elsevier Science BV
ISSN
1570-9639
NCID
出版者DOI
言語
英語
NII資源タイプ
学術雑誌論文
広大資料タイプ
学術雑誌論文
DCMIタイプ
text
フォーマット
application/pdf
著者版フラグ
author
権利情報
(c) 2012 Elsevier B.V. All rights reserved.
関連情報URL
部局名
理学研究科