10.1021/bi051672a.s001
Christopher P. Jaroniec
Christopher P.
Jaroniec
Joshua D. Kaufman
Joshua D.
Kaufman
Stephen J. Stahl
Stephen J.
Stahl
Mathias Viard
Mathias
Viard
Robert Blumenthal
Robert
Blumenthal
Paul T. Wingfield
Paul T.
Wingfield
Ad Bax
Ad
Bax
Structure and Dynamics of Micelle-Associated Human Immunodeficiency Virus
gp41 Fusion Domain<sup>†</sup><sup>,</sup><sup>‡</sup>
American Chemical Society
2005
NMR
nanosecond time scale dynamics
residue
Backbone amide 15 N
micelle
HSQC
amide hydrogen exchange rates
NOE
LPPG
15 N
DPC
HIV
gp 41 envelope glycoprotein
SDS
fusion
2005-12-13 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Structure_and_Dynamics_of_Micelle_Associated_Human_Immunodeficiency_Virus_gp41_Fusion_Domain_sup_sup_sup_sup_sup_sup_/3251974
The N-terminal fusion domain of the HIV-1 gp41 envelope glycoprotein is responsible for
initiating the fusion of viral and cellular membranes, leading to the subsequent infection of the host cell
by HIV-1. We have investigated the backbone structure and dynamics of the 30 N-terminal residues of
HIV-1 gp41 in membrane-mimicking environments using NMR spectroscopy and <sup>15</sup>N- and <sup>15</sup>N,<sup>13</sup>C,<sup>2</sup>H-labeled peptides. Similar <sup>15</sup>N−<sup>1</sup>H HSQC spectra were obtained in a variety of detergents, including SDS,
DPC, mixed DPC/SDS, and LPPG micelles, indicating that the peptide structure is not strongly influenced
by the type of detergent used. Detailed characterization was carried out in SDS micelles, where the long-term sample stability was found to be optimal. In addition to <i>J</i>-coupling and NOE restraints, a nearly
complete set of backbone residual dipolar coupling restraints was recorded for the fusion domain−micelle
complex aligned with respect to the magnetic field using a stretched polyacrylamide gel. Backbone amide
<sup>15</sup>N spin relaxation and amide hydrogen exchange rates with the solvent were also measured. The ensemble
of NMR structures reveals an uninterrupted α-helix for the least mobile residues (<b><i>S</i></b><sup>2</sup> > 0.65), Ile-4 to
Met-19, with transient helical character extending up to Ala-22. A 12-residue (Ile-4 to Ala-15) segment
is fully shielded from solvent, with Gly-3 and Gly-16 found at micelle−solvent interfaces. Residues external
to the micelle exhibit enhanced picosecond to nanosecond time scale dynamics relative to the residues
buried in the micelle, and their mobility increases with the distance from the micelle.