Autonomous folding in the membrane proximal HIV peptide gp41(659-671): pH tuneability at micelle interfaces.
The flexibility of the Membrane Proximal Region (MPR) of the HIV-1 gp41 envelope glycoprotein is believed to be relevant to its biological function. Its conformational bias is potentially influenced by the various environmental conditions experienced during viral fusion. Using a combination of Circular Dichroism and Molecular Dynamics simulations, we show that a very short MPR fragment gp41(659-671) spanning the 2F5 monoclonal antibody epitope, exhibits autonomous helical folding in the presence of membrane mimicking SDS micelles and the extent of which can be tuned by pH variation: Specifically, the peptide shows no defined fold type at basic pH but is helical at physiological and lower pH environments. By contrast, no such control of helical folding by pH is observed in aqueous solutions in the absence of SDS. Instead, the experimental data imply that unfolded structures persist and that pH has negligible influence on conformational bias. We also explore the pronounced sensitivity to standard empirical potentials and conclude that AMBER-ff03 provides a reasonably accurate description of the solution state structure and is therefore a good choice for future exploration of membrane-induced phenomena.
School of Physics, The University of Edinburgh, Mayfield Road, Edinburgh, EH9 3JZ, UK. c.r.gregor-2@sms.ed.ac.uk
Craig R
CR
Gregor
Eleonora
E
Cerasoli
Paul R
PR
Tulip
Maxim G
MG
Ryadnov
Glenn J
GJ
Martyna
Jason
J
Crain
D000911:Antibodies, Monoclonal / Q000737:chemistry; D002942:Circular Dichroism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008567:Membranes, Artificial; D008823:Micelles; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D017510:Protein Folding
D000911:Antibodies, Monoclonal; D015700:HIV Envelope Protein gp41; D008567:Membranes, Artificial; D008823:Micelles