Grafting Segments from the Extracellular Surface of CCR5 onto a Bacteriorhodopsin Transmembrane Scaffold Confers HIV-1 Coreceptor Activity

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• 作者：Abdulaev ; Najmoutin G. ; Strassmaier ; Timothy T. ; Ngo ; Tony ; Chen ; Ruiwu ; Luecke ; Hartmut ; Oprian ; Daniel D. ; et. al.
• 关键词：bacteriorhodopsin ; CCR5 ; chimera ; G protein-coupled receptor ; HIV-1 ; membrane protein folding
• 刊名：Structure
• 出版年：2002
• 出版时间：April, 2002
• 年：2002
• 卷：10
• 期：4
• 页码：515-525
• 全文大小：371 K

文摘

Components from the extracellular surface of CCR5 interact with certain macrophage-tropic strains of human immunodeficiency virus type 1 (HIV-1) to mediate viral fusion and entry. To mimic these viral interacting site(s), the amino-terminal and extracellular loop segments of CCR5 were linked in tandem to form concatenated polypeptides, or grafted onto a seven-transmembrane bacteriorhodopsin scaffold to generate several chimeras. The chimera studies identified specific regions in CCR5 that confer HIV-1 coreceptor function, structural rearrangements in the transmembrane region that may modulate this activity, and a role for the extracellular surface in folding and assembly. Methods developed here may be applicable to the dissection of functional domains from other seven-transmembrane receptors and form a basis for future structural studies.