Membrane structure correlates to function of LLP2 on the cytoplasmic tail of HIV-1 gp41 protein.
Mutation studies previously showed that the lentivirus lytic peptide (LLP2) sequence of the cytoplasmic C-terminal tail of the HIV-1 gp41 envelope protein inhibited viral-initiated T-cell death and T-cell syncytium formation, at which time in the HIV life cycle the gp41 protein is embedded in the T-cell membrane. In striking contrast, the mutants did not affect virion infectivity, during which time the gp41 protein is embedded in the HIV envelope membrane. To examine the role of LLP2/membrane interactions, we applied synchrotron x-radiation to determine structure of hydrated membranes. We focused on WT LLP2 peptide (+3 charge) and MX2 mutant (-1 charge) with membrane mimics for the T-cell and the HIV-1 membranes. To investigate the influence of electrostatics, cholesterol content, and peptide palmitoylation, we also studied three other LLP2 variants and HIV-1 mimics without negatively charged lipids or cholesterol as well as extracted HIV-1 lipids. All LLP2 peptides bound strongly to T-cell membrane mimics, as indicated by changes in membrane structure and bending. In contrast, none of the weakly bound LLP2 variants changed the HIV-1 membrane mimic structure or properties. This correlates well with, and provides a biophysical basis for, previously published results that reported lack of a mutant effect in HIV virion infectivity in contrast to an inhibitory effect in T-cell syncytium formation. It shows that interaction of LLP2 with the T-cell membrane modulates biological function.
Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
Alexander L
AL
Boscia
Kiyotaka
K
Akabori
Zachary
Z
Benamram
Jonathan A
JA
Michel
Michael S
MS
Jablin
Jonathan D
JD
Steckbeck
Ronald C
RC
Montelaro
John F
JF
Nagle
Stephanie
S
Tristram-Nagle
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry; D006801:Humans; D054878:Lipoylation; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D013601:T-Lymphocytes / Q000378:metabolism
D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; C116049:lentiviral lytic peptide type 1, Human immunodeficiency virus 1; D002784:Cholesterol