Secondary Structure Determination of gp41(659-671)

The short 13-residue fragment of the human HIV-1 surface glycoprotein (peptide gp41(659671)) is special in several respects: Primarily it comprises the only sequential epitope for one of the known antibodies of HIV-1. Recent findings indicate that rather than the peptide adopting one dominant structure, several motifs compete with one another and that the peptide has a high conformational plasticity. Established techniques such as Circular Dichroism (CD) and Molecular Dynamics (MD) are used in ascertaining the native secondary structure of gp41(659671) and exploring the sensitivity of its secondary structure to changes in the environment. The results support previously published findings that suggest the secondary structure of gp41(659671) under ambient conditions is comprised of a flexible conformational ensemble. Furthermore, this ensemble becomes biased towards a helical motif in a membrane-mimicking environment. It is proposed that the main driving force of this structural change is the promotion of intramolecular hydrogen bonding, while electrostatic interactions serve as a stabilisation mechanism.