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 α-helical structure. The infrared dichroism data of the 13C- labeled peptide yielded a helix tilt β = (6.5 ± 1.7)°from the membrane normal. The rotational pitch angle ω, defined as zero for a residue located in the direction of the helix tilt, is ω = (283 ± 11)°for the 13C labels Val13/Val20 and ω = (23 ± 11)°for the 13C labels Ala14/Val21. 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.
Original language | American English |
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Pages (from-to) | 1594-1601 |
Number of pages | 8 |
Journal | Biophysical Journal |
Volume | 77 |
Issue number | 3 |
DOIs | |
State | Published - Sep 1999 |
Externally published | Yes |
Bibliographical note
Funding Information:This work was supported by grants from the Welcome Trust and the BBSRC.