title: A trimeric structural subdomain of the HIV-1 transmembrane glycoprotein.
abstract: HIV-1 infection is initiated by the fusion of viral and cellular membranes with subsequent transfer of viral genetic material into the cell. The HIV-1 transmembrane envelope glycoprotein gp41 plays a major role in this membrane fusion process. Previous studies have shown that a stable, alpha-helical, trimeric structural domain of gp41 consists of N-terminal 51-residue (N-51) and C-terminal 43-residue (C-43) extraviral segments. This alpha-helical, trimeric complex has been proposed to form the core of the membrane fusion-active conformation of the HIV-1 envelope. We show here that a stable subdomain can be formed by shorter 36-residue (N-36) and 34-residue (C-34) peptides corresponding to the central regions of N-51 and C-43, respectively. In isolation, N-36 is predominantly aggregated, while C-34 is unfolded. Upon mixing, however, these peptides form a stable, alpha-helical, discrete trimer of heterodimers (the melting temperature of a 10 microM solution is 64 degrees C at pH 7). Thus, this subdomain displays the salient features of the stable core structure of the isolated gp41 protein. Our results also provide strong support for the notion that short peptides can form unique, cooperatively folded subdomains, in which elements of secondary structure are stabilized by native-like tertiary interactions.
authors.affiliation: Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge 02142, USA. mlu@mail.med.cornell.edu
authors.forename: M
authors.initials: M
authors.lastname: Lu
authors.forename: P S
authors.initials: PS
authors.lastname: Kim
mesh_terms: D019286:Endopeptidase K / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000737:chemistry
chemical_list: D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D010455:Peptides; D019286:Endopeptidase K