Membrane mediated regulation in free peptides of HIV-1 gp41: minimal modulation of the hemifusion phase.

Membrane-mediated structural modulation in two short fragments of the human HIV-1 envelope protein gp41 is demonstrated. Derived from the C-terminal membrane proximal external (MPE) and N-terminal fusion peptide proximal (FPP) regions, these peptides are widely separated in the primary sequence but form tertiary contacts during the intermediate (hemifusion) phase of HIV infection. The structural perturbations observed at the membrane interface offer evidence of rudimentary regulatory mechanisms operating in the free peptides which may be relevant in the biological system.

Antibody recognition of a human chorionic gonadotropin epitope (hCGbeta66-80) depends on local structure retained in the free peptide.

Human chorionic gonadotropin (hCG) is an important biomarker in pregnancy and oncology, where it is routinely detected and quantified by specific immunoassays. Intelligent epitope selection is essential to achieving the required assay performance. We present binding affinity measurements demonstrating that a typical β3-loop-specific monoclonal antibody (8G5) is highly selective in competitive immunoassays and distinguishes between hCGβ(66-80) and the closely related luteinizing hormone (LH) fragment LHβ(86-100), which differ only by a single amino acid residue.

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.