Solid-state nuclear magnetic resonance measurements of HIV fusion peptide to lipid distances reveal the intimate contact of beta strand peptide with membranes and the proximity of the Ala-14-Gly-16 region with lipid headgroups.
Human immunodeficiency virus (HIV) infection begins with fusion between viral and host cell membranes and is catalyzed by the HIV gp41 fusion protein. The approximately 20 N-terminal apolar residues of gp41 are called the HIV fusion peptide (HFP), interact with the host cell membrane, and play a key role in fusion. In this study, the membrane location of peptides which contained the HFP sequence (AVGIGALFLGFLGAAGSTMGARS) was probed in samples containing either only phospholipids or phospholipids and cholesterol. Four HFPs were examined which each contained 13CO labeling at three sequential residues between G5 and G16. The 13CO chemical shifts indicated that HFP had predominant beta strand conformation over the labeled residues in the samples. The internuclear distances between the HFP 13CO groups and the lipid 31P atoms were measured using solid-state nuclear magnetic resonance rotational-echo double-resonance experiments. The shortest 13CO-31P distances of 5-6 A were observed for HFP labeled between A14 and G16 and correlated with intimate association of beta strand HFP and membranes. These results were confirmed with measurements using HFPs singly labeled with 13CO at A6 or A14. To our knowledge, these data are the first measurements of distances between HIV fusion peptide nuclei and lipid P, and qualitative models of the membrane location of oligomeric beta strand HFP which are consistent with the experimental data are presented. Observation of intimate contact between beta strand HFP and membranes provides a rationale for further investigation of the relationship between structure and fusion activity for this conformation.
Qiang
Wei
W
Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, USA.
Yang
Jun
J
Weliky
David P
DP
D000409:Alanine / Q000737:chemistry*; D000595:Amino Acid Sequence; D005998:Glycine / Q000737:chemistry*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism
D015700:HIV Envelope Protein gp41; D008055:Lipids; D010446:Peptide Fragments; D000409:Alanine; D005998:Glycine