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Conformational transition of membrane-associated terminally acylated HIV-1 Nef.


ABSTRACT: Many proteins are posttranslationally modified by acylation targeting them to lipid membranes. While methods such as X-ray crystallography and nuclear magnetic resonance are available to determine the structure of folded proteins in solution, the precise position of folded domains relative to a membrane remains largely unknown. We used neutron and X-ray reflection methods to measure the displacement of the core domain of HIV Nef from lipid membranes upon insertion of the N-terminal myristate group. Nef is one of several HIV-1 accessory proteins and an essential factor in AIDS progression. Upon insertion of the myristate and residues from the N-terminal arm, Nef transitions from a closed-to-open conformation that positions the core domain 70 Å from the lipid headgroups. This work rules out previous speculation that the Nef core remains closely associated with the membrane to optimize interactions with the cytoplasmic domain of MHC-1.

SUBMITTER: Akgun B 

PROVIDER: S-EPMC4011395 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Conformational transition of membrane-associated terminally acylated HIV-1 Nef.

Akgun Bulent B   Satija Sushil S   Nanda Hirsh H   Pirrone Gregory F GF   Shi Xiaomeng X   Engen John R JR   Kent Michael S MS  

Structure (London, England : 1993) 20130912 10


Many proteins are posttranslationally modified by acylation targeting them to lipid membranes. While methods such as X-ray crystallography and nuclear magnetic resonance are available to determine the structure of folded proteins in solution, the precise position of folded domains relative to a membrane remains largely unknown. We used neutron and X-ray reflection methods to measure the displacement of the core domain of HIV Nef from lipid membranes upon insertion of the N-terminal myristate gro  ...[more]

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