Lee C H, Saksela K, Mirza U A, Chait B T, Kuriyan J
The Rockefeller University, New York, New York 10021, USA.
Cell. 1996 Jun 14;85(6):931-42. doi: 10.1016/s0092-8674(00)81276-3.
The crystal structure of the conserved core of HIV-1 Nef has been determined in complex with the SH3 domain of a mutant Fyn tyrosine kinase (a single amino acid substitution, Arg-96 to isoleucine), to which Nef binds tightly. The conserved PxxP sequence motif of Nef, known to be important for optimal viral replication, is part of a polyproline type II helix that engages the SH3 domain in a manner resembling closely the interaction of isolated peptides with SH3 domains. The Nef-SH3 structure also reveals how high affinity and specificity in the SH3 interaction is achieved by the presentation of the PxxP motif within the context of the folded structure of Nef.
已确定HIV-1 Nef保守核心的晶体结构，它与突变型Fyn酪氨酸激酶的SH3结构域（单个氨基酸取代，精氨酸96突变为异亮氨酸）形成复合物，Nef与该结构域紧密结合。Nef保守的PxxP序列基序，已知对最佳病毒复制很重要，它是II型多聚脯氨酸螺旋的一部分，该螺旋与SH3结构域的结合方式与分离肽与SH3结构域的相互作用极为相似。Nef-SH3结构还揭示了在Nef折叠结构的背景下呈现PxxP基序是如何实现SH3相互作用中的高亲和力和特异性的。
