title: vpu transmembrane peptide structure obtained by site-specific fourier transform infrared dichroism and global molecular dynamics searching.
abstract: The recently developed method of site-directed Fourier transform infrared dichroism for obtaining orientational constraints of oriented polymers is applied here to the transmembrane domain of the vpu protein from the human immunodeficiency virus type 1 (HIV-1). The infrared spectra of the 31-residue-long vpu peptide reconstituted in lipid vesicles reveal a predominantly alpha-helical structure. The infrared dichroism data of the (13)C-labeled peptide yielded a helix tilt beta = (6.5 +/- 1.7) degrees from the membrane normal. The rotational pitch angle omega, defined as zero for a residue located in the direction of the helix tilt, is omega = (283 +/- 11) degrees for the (13)C labels Val(13)/Val(20) and omega = (23 +/- 11) degrees for the (13)C labels Ala(14)/Val(21). A global molecular dynamics search protocol restraining the helix tilt to the experimental value was performed for oligomers of four, five, and six subunits. From 288 structures for each oligomer, a left-handed pentameric coiled coil was obtained, which best fits the experimental data. The structure reveals a pore occluded by Trp residues at the intracellular end of the transmembrane domain.
authors.affiliation: Cambridge Center for Molecular Recognition, Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, England.
authors.forename: A
authors.initials: A
authors.lastname: Kukol
authors.forename: I T
authors.initials: IT
authors.lastname: Arkin
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D015497:HIV-1 / Q000737:chemistry; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry*; D000086082:Viroporin Proteins
chemical_list: D054298:Human Immunodeficiency Virus Proteins; D010446:Peptide Fragments; D010455:Peptides; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins