CONFORMATIONS OF THE HIV1 ENVELOPE GLYCOPROTEIN

描述(改编自申请人的摘要)：本提案的目标 是为了了解HIV的构象和构象转变 包膜糖蛋白。X射线结晶学分析将是 主要方法。Gpl4O的结构，低聚物(可能是 Gpl6O的三聚体)胞外结构域是一个主要的焦点。申请者可以出示 SIV gpl4O大量生产，并将继续努力使其结晶在 与CD4(双域片段)和特定Fab的复合体。他们提议 通过添加三聚体“异亮氨酸”来稳定分泌的HIV gpl4O 或通过突变gp4l中的某些残基 部分给他们(更稳定的)SIV对应者。他们还将把艾滋病毒与 Gpl2O到三聚化拉链，类似的目标是研究gp120作为 齐聚物。他们将继续努力使三元系结晶。 Gpl2O与CD4和各种Fab的络合物--HIV的结构 包膜糖蛋白对许多疫苗都很重要。 战略。理解HIV抗原性的三维框架 变化显然是一个重要的目标。

DESCRIPTION (adapted from applicant's abstract): The goal of this proposal is to understand the conformations and conformational transitions of the HIV envelope glycoprotein. X-ray crystallographic analysis will be the principal approach. The structure of gpl4O, the oligomeric (probably trimeric) ectodomain of gpl6O, is a major focus. The applicants can produce SIV gpl4O in large quantities, and will pursue efforts to crystallize it in complex with CD4 (two-domain fragment) and with a specific Fab. They propose to stabilize secreted HIV gpl4O by addition of a trimerizing "isoleucine zipper" at its C-terminus or by mutating certain residues in the gp4l portion to their (more stable) SIV counterparts. They will also link HIV gpl2O to trimerizing zippers, with the similar goal of studying gp120 as an oligomer. They will continue on-going efforts to crystallize ternary complexes of gpl2O with CD4 and various Fab's. The structure of the HIV envelope glycoprotein is of fundamental importance to many vaccine strategies. A three-dimensional framework for understanding HIV antigenic variation is clearly a significant goal.