2NV3

Solution structure of L8A mutant of HIV-1 myristoylated matrix protein

2NV3 の概要

• エントリーDOI: 10.2210/pdb2nv3/pdb
• 関連するPDBエントリー: 2H3I 2JMG
• 分子名称: Gag polyprotein, MYRISTIC ACID (2 entities in total)
• 機能のキーワード: l8a mutant of hiv-1 myristoylated matrix protein, viral protein
• 由来する生物種: Human immunodeficiency virus 1
• 細胞内の位置: Matrix protein p17: Virion (By similarity): Q72497
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14920.90

構造登録者

Saad, J.S.,Loeliger, E.,Luncsford, P.,Liriano, M.,Tai, J.,Kim, A.,Miller, J.,Joshi, A.,Freed, E.O.,Summers, M.F. (登録日: 2006-11-10, 公開日: 2007-02-06, 最終更新日: 2024-10-30)

主引用文献

Saad, J.S.,Loeliger, E.,Luncsford, P.,Liriano, M.,Tai, J.,Kim, A.,Miller, J.,Joshi, A.,Freed, E.O.,Summers, M.F.
Point mutations in the HIV-1 matrix protein turn off the myristyl switch.
J.Mol.Biol., 366:574-585, 2007

PubMed Abstract: During the late phase of human immunodeficiency virus type-1 (HIV-1) replication, newly synthesized retroviral Gag proteins are targeted to lipid raft regions of specific cellular membranes, where they assemble and bud to form new virus particles. Gag binds preferentially to the plasma membrane (PM) of most hematopoietic cell types, a process mediated by interactions between the cellular PM marker phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P(2)) and Gag's N-terminally myristoylated matrix (MA) domain. We recently demonstrated that PI(4,5)P(2) binds to a conserved cleft on MA and promotes myristate exposure, suggesting a role as both a direct membrane anchor and myristyl switch trigger. Here we show that PI(4,5)P(2) is also capable of binding to MA proteins containing point mutations that inhibit membrane binding in vitro, and in vivo, including V7R, L8A and L8I. However, these mutants do not exhibit PI(4,5)P(2) or concentration-dependent myristate exposure. NMR studies of V7R and L8A MA reveal minor structural changes that appear to be responsible for stabilizing the myristate-sequestered (myr(s)) species and inhibiting exposure. Unexpectedly, the myristyl group of a revertant mutant with normal PM targeting properties (V7R,L21K) is also tightly sequestered and insensitive to PI(4,5)P(2) binding. This mutant binds PI(4,5)P(2) with twofold higher affinity compared with the native protein, suggesting a potential compensatory mechanism for membrane binding.

PubMed: 17188710
DOI: 10.1016/j.jmb.2006.11.068

実験手法

SOLUTION NMR