title: 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.
authors.affiliation: National Institute of Standards and Technology, Gaithersburg, MD 20899, USA; Department of Materials Science and Engineering, University of Maryland, College Park, MD 20742, USA; Department of Chemistry, Boğaziçi University, Bebek 34342, Istanbul, Turkey.
authors.forename: Bulent
authors.initials: B
authors.lastname: Akgun
authors.forename: Sushil
authors.initials: S
authors.lastname: Satija
authors.forename: Hirsh
authors.initials: H
authors.lastname: Nanda
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Pirrone
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Shi
authors.forename: John R
authors.initials: JR
authors.lastname: Engen
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kent
mesh_terms: D000215:Acylation; D000327:Adsorption; D020816:Amino Acid Motifs; D015497:HIV-1; D008567:Membranes, Artificial; D008958:Models, Molecular; D033363:Neutron Diffraction; D010715:Phosphatidylglycerols / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D014961:X-Ray Diffraction; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000737:chemistry*
chemical_list: D008567:Membranes, Artificial; D010715:Phosphatidylglycerols; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; C030345:1,2-dipalmitoylphosphatidylglycerol
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