3VLG

Crystal structure of the W150A mutant LOX-1 CTLD showing impaired OxLDL binding

Summary for 3VLG

• Entry DOI: 10.2210/pdb3vlg/pdb
• Related: 1YXJ 1YXK
• Descriptor: Oxidized low-density lipoprotein receptor 1 (2 entities in total)
• Functional Keywords: c-type lectin-like domain, oxidized ldl receptor, membrane protein, lipid binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Single-pass type II membrane protein: P78380
• Total number of polymer chains: 1
• Total formula weight: 16320.61

Authors

Nakano, S.,Sugihara, M.,Yamada, R.,Katayanagi, K.,Tate, S. (deposition date: 2011-12-01, release date: 2012-04-18, Last modification date: 2024-10-30)

Primary citation

Nakano, S.,Sugihara, M.,Yamada, R.,Katayanagi, K.,Tate, S.
Structural implication for the impaired binding of W150A mutant LOX-1 to oxidized low density lipoprotein, OxLDL
Biochim.Biophys.Acta, 1824:739-749, 2012

PubMed 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.

PubMed: 22369967
DOI: 10.1016/j.bbapap.2012.02.003

Experimental method

X-RAY DIFFRACTION (2.3 Å)