Dynamics Study on the Anti-Human Immunodeficiency Virus Chemokine Viral Macrophage-Inflammatory Protein-II (VMIP-II) Reveals a Fully Monomeric Protein

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• 作者：Andy C. LiWang ; Jian Jing Cao ; Hong Zheng ; Zhaohai Lu ; Stephen C. Peiper ; and Patricia J. LiWang
• 刊名：Biochemistry
• 出版年：1999
• 出版时间：January 5, 1999
• 年：1999
• 卷：38
• 期：1
• 页码：442 - 453
• 全文大小：148K
• 年卷期：v.38,no.1(January 5, 1999)
• ISSN：1520-4995

文摘

Encoded by Kaposi's sarcoma-associated herpesvirus, viral macrophage-inflammatory protein-II (VMIP-II) is unique among CC chemokines in that it has been shown to bind to the CXC chemokinereceptor CXCR4 as well as to a variety of CC chemokine receptors. This unique binding ability allowsvMIP-II to block infection by a wide range of human immunodeficiency virus type I (HIV-1) strains, butthe structural and dynamic basis for this broad range of binding is not known. ¹⁵N T₁, T₂ and ¹⁵N{-H^N}nuclear Overhauser effect (NOE) values of vMIP-II, determined through a series of heteronuclearmultidimensional nuclear magnetic resonance (NMR) experiments, were used to obtain information aboutthe backbone dynamics of the protein. Whereas almost all chemokine structures reveal a dimer or multimer,vMIP-II has a rotational correlation time (mages/gifchars/tau.gif" BORDER=0 >_c) of 4.7 ± 0.3 ns, which is consistent with a monomericchemokine. The rotational diffusion anisotropy, D_{mages/entities/par.gif">}/D_{mages/entities/bottom.gif">}, is approximately 1.5 ± 0.1. The conformation ofvMIP-II is quite similar to other known chemokines, containing an unstructured N-terminus followed byan ordered turn, three mages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-strands arranged in an antiparallel fashion, and one C-terminal mages/gifchars/alpha.gif" BORDER=0>-helix that liesacross the mages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-strands. Most of the protein is well-ordered on a picosecond time scale, with an averageorder parameter S² (excluding the N-terminal 13 amino acids) of 0.83 ± 0.09, and with even greaterorder in regions of secondary structure. The NMR data reveal that the N-terminus, which in otherchemokines has been implicated in receptor binding, extends like a flexible tail in solution and possessesno secondary structure. The region of the ordered turn, including residues 25-28, experiencesconformational exchange dynamics. The implications of these NMR data to the broad receptor bindingcapability of vMIP-II are discussed.