Journal of Biochemistry Advance Access originally published online on April 6, 2007
Journal of Biochemistry 2007 141(6):855-866; doi:10.1093/jb/mvm093
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© 2007 The Japanese Biochemical Society.
Chimeric Structural Stabilities in the Coiled-Coil Structure of the NECK Domain in Human Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1 (LOX-1)
1Department of Structural Biology, Biomolecular Engineering Research Institute (BERI), 6-2-3, Furuedai, Suita, Osaka 565-0874; 2Research Institute of Pharmaceutical Science, Musashino University, 1-1-20 Shinmachi Nishitokyo-shi, Tokyo 202-8585; and 3PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho Kawaguchi, Saitama, Japan
*To whom correspondence should be addressed. Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526, Japan. Tel: +81-82-424-7387, Fax: +81-82-424-7387, E-mail: tate{at}hiroshima-u.ac.jp
Received February 25, 2007; Accepted March 30, 2007
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Abstract |
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LOX-1 (lectin-like oxidized low-density lipoprotein receptor 1) is the major oxidized LDL (OxLDL) receptor on endothelial cells. The extracellular part of LOX-1 comprises an 82-residue stalk region (NECK) and a C-type lectin-like ligand-binding domain (CTLD). The NECK displays sequence similarity to the coiled-coil region of myosin, having been suggested it adopts a rod-like structure. In this article, we report the structural analyses of human LOX-1 NECK using a variety of approaches including limited proteolysis, chemical cross-linking, circular dichroism (CD) and NMR. Our analysis reveals a unique structural feature of the LOX-1 NECK. Despite significant sequence similarity with the myosin coiled-coil, LOX-1 NECK does not form a uniform rod-like structure. Although not random, one-third of the N-terminal NECK is less structured than the remainder of the protein and is highly sensitive to cleavage by a variety of proteases. The coiled-coil structure is localized at the C-terminal part of the NECK, but is in dynamic equilibrium among multiple conformational states on a µs–ms time scale. This chimeric structural property of the NECK region may enable clustered LOX-1 on the cell surface to recognize OxLDL.
Key Words: atherosclerosis, LDL, membrane proteins, CD, NMR
Abbreviations: CD, circular dichroism; CTLD, C-type lectin-like ligand-binding domain; DC-SIGN, dendritic cell-specific ICAM-3 grabbing nonintegrin; DTT, dithiothreitol; HSQC, heteronuclear single quantum coherence spectroscopy; LDL, low-density lipoprotein; MALDI-TOF, matrix-assisted laser desorption ionization time-of-flight; MS, mass spectrometry; NMR, nuclear magnetic resonance; SDS–PAGE, sodium dodecyl sulphate polyacrylamide gel electrophoresis
Present address: Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526, Japan.
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