Dataset Information

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

ACCESS DATA

Publications

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]

PMID: 24035710

Similar Datasets

Project description:Intrinsically disordered proteins represent a class of proteins that lack fixed and well-defined three-dimensional structures in solution. HIV-1 Nef is an intrinsically disordered peripheral membrane protein involved in the replication and pathogenesis of HIV-1 infection. Nef controls expression levels of cell surface CD4 molecules that are essential for adaptive immunity. Despite the lack of fixed and stable structures, Nef physically interacts with the host cellular proteins (AP-1/MHC-I) and modulates intracellular trafficking pathways. Therefore, it is essential to understand how this dynamic conformational flexibility affects Nef structures and function. In this study, we combined all-atom molecular dynamics (MD) simulations and dynamic network approaches to better understand the structure and dynamics of Nef in two different forms, the free unbound and the bound state. Using the MD simulation approach, we show that the intrinsically disordered Nef exhibit a large dynamic field with more atomic fluctuations and lesser thermodynamic stability in the unbound conditions. The conformations of Nef change over time, and this protein remains more compact, folded, and stable in the bound form. The dynamic network analysis revealed regions of the protein capable of modulating the conformational behavior of the disordered Nef. The average betweenness centrality (BC) unveiled residues that are critical for mediating protein-protein interactions. The average shortest path length (L) and the perturbation response scanning exposed residues that are likely to be important in steering protein conformational changes. Overall, the study demonstrates how all-atom MD simulations combined with the dynamic network approach can be used to gain further insights into the structure and dynamics-function relationship of intrinsically disordered HIV-1 Nef.Supplementary informationThe online version contains supplementary material available at 10.1007/s13205-021-02698-8.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets