N-linked glycosylation in the CXCR4 N-terminus inhibits binding to HIV-1 envelope glycoproteins

详细信息    查看全文

• 作者：Wang ; Jianbin ; Babcock ; Gregory J. ; Choe ; Hyeryun ; Farzan ; Michael ; Sodroski ; Joseph ; Gabuzda ; Dana
• 关键词：Human immunodeficiency virus (HIV-1) ; Envelope glycoprotein (gp120) ; CXCR4 ; Paramagnetic proteoliposomes (PMPLs) ; N-linked glycosylation ; Stromal cell-derived factor (SDF)-1α
• 刊名：Virology
• 出版年：2004
• 出版时间：June 20, 2004
• 年：2004
• 卷：324
• 期：1
• 页码：140-150
• 全文大小：647 K

文摘

CXCR4 is a co-receptor along with CD4 for human immunodeficiency virus type 1 (HIV-1). We investigated the role of N-linked glycosylation in the N-terminus of CXCR4 in binding to HIV-1 gp120 envelope glycoproteins. Gp120s from CXCR4 (X4) and CCR5 (R5) using HIV-1 strains bound more efficiently to non-N-glycosylated than to N-glycosylated CXCR4 proteoliposomes in a CD4-dependent manner. Similar results were observed in binding studies using non-N-glycosylated or N-glycosylated CXCR4 expressed on cells. Mutation of the N-glycosylation site N11 in CXCR4 (N11Q-CXCR4) enhanced CD4-dependent binding of X4 and R5 gp120s and allowed more efficient entry of viruses pseudotyped with X4 or R5 HIV-1 envelope glycoproteins. However, the binding of R5 gp120 to N11Q-CXCR4 and entry of R5 HIV-1 viruses into cells expressing N11Q-CXCR4 were 20- and 100- to 1000-fold less efficient, respectively, than the levels achieved using X4 gp120 or X4 HIV-1 viruses. Binding of stromal cell-derived factor (SDF)-1α, the natural ligand of CXCR4, and SDF-1α-induced signaling were reduced by the N11Q mutation. These findings demonstrate that N-glycosylation at N11 inhibits the binding of CXCR4 to X4 and R5 HIV-1 gp120, and provide a better understanding of the structural elements of CXCR4 involved in HIV-1 Env–co-receptor interactions.