与HIV-1 p6蛋白的PTAP基序结合的Tsg101 UEV结构域的结构。

Structure of the Tsg101 UEV domain in complex with the PTAP motif of the HIV-1 p6 protein.

作者信息

Pornillos Owen, Alam Steven L, Davis Darrell R, Sundquist Wesley I

机构信息

Department of Biochemistry, University of Utah, Salt Lake City, Utah 84132, USA.

出版信息

Nat Struct Biol. 2002 Nov;9(11):812-7. doi: 10.1038/nsb856.

DOI:10.1038/nsb856

PMID:12379843

Abstract

The structural proteins of HIV and Ebola display PTAP peptide motifs (termed 'late domains') that recruit the human protein Tsg101 to facilitate virus budding. Here we present the solution structure of the UEV (ubiquitin E2 variant) binding domain of Tsg101 in complex with a PTAP peptide that spans the late domain of HIV-1 p6(Gag). The UEV domain of Tsg101 resembles E2 ubiquitin-conjugating enzymes, and the PTAP peptide binds in a bifurcated groove above the vestigial enzyme active site. Each PTAP residue makes important contacts, and the Ala 9-Pro 10 dipeptide binds in a deep pocket of the UEV domain that resembles the X-Pro binding pockets of SH3 and WW domains. The structure reveals the molecular basis of HIV PTAP late domain function and represents an attractive starting point for the design of novel inhibitors of virus budding.

摘要

人类免疫缺陷病毒（HIV）和埃博拉病毒的结构蛋白呈现出PTAP肽基序（称为“晚期结构域”），该基序可招募人类蛋白Tsg101以促进病毒出芽。在此，我们展示了Tsg101的泛素E2变体（UEV）结合结构域与跨越HIV-1 p6（Gag）晚期结构域的PTAP肽形成复合物的溶液结构。Tsg101的UEV结构域类似于E2泛素结合酶，PTAP肽结合在残余酶活性位点上方的分叉凹槽中。PTAP的每个残基都形成重要的接触，丙氨酸9-脯氨酸10二肽结合在UEV结构域的一个深口袋中，该口袋类似于SH3和WW结构域的X-脯氨酸结合口袋。该结构揭示了HIV PTAP晚期结构域功能的分子基础，并为设计新型病毒出芽抑制剂提供了一个有吸引力的起点。