title: Broad distribution of energetically important contacts across an extended protein interface.
abstract: Infection of cells by HIV depends upon profound structural rearrangements within the trimeric viral protein gp41. Critical to this process is the formation of a six-helix bundle in which a set of three N-terminal heptad repeat (NHR) helices assemble to form a core displaying long grooves that provide docking sites for three C-terminal heptad repeat (CHR) helices. We report experiments designed to discriminate between two alternative hypotheses regarding the source of affinity between individual CHR helices and the complementary groove: (1) affinity is dominated by interactions of a small cluster of side chains at one end of the CHR helix; or (2) affinity depends upon interactions distributed across the long CHR helix. We have employed two complementary experimental designs, and results from both favor the latter hypothesis.
authors.affiliation: Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Johnson
authors.forename: W Seth
authors.initials: WS
authors.lastname: Horne
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Gellman
mesh_terms: D000595:Amino Acid Sequence; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D020449:Repetitive Sequences, Amino Acid; D013499:Surface Properties; D013816:Thermodynamics
chemical_list: D015700:HIV Envelope Protein gp41; C514787:gp41 protein, Human immunodeficiency virus 1