Structure of the amino-terminal core domain of the HIV-1 capsid protein.
The three-dimensional structure of the amino-terminal core domain (residues 1 through 151) of the human immunodeficiency virus-type 1 (HIV-1) capsid protein has been solved by multidimensional heteronuclear magnetic resonance spectroscopy. The structure is unlike those of previously characterized viral coat proteins and is composed of seven alpha helices, two beta hairpins, and an exposed partially ordered loop. The domain is shaped like an arrowhead, with the beta hairpins and loop exposed at the trailing edge and the carboxyl-terminal helix projecting from the tip. The proline residue Pro1 forms a salt bridge with a conserved, buried aspartate residue (Asp51), which suggests that the amino terminus of the protein rearranges upon proteolytic maturation. The binding site for cyclophilin A, a cellular rotamase that is packaged into the HIV-1 virion, is located on the exposed loop and encompasses the essential proline residue Pro90. In the free monomeric domain, Pro90 adopts kinetically trapped cis and trans conformations, raising the possibility that cyclophilin A catalyzes interconversion of the cis- and trans-Pro90 loop structures.
Gitti
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Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Maryland Baltimore County, Baltimore, MD 21228, USA.
Lee
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Walker
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Summers
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Yoo
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Sundquist
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D000591:Amino Acid Isomerases / Q000378:metabolism; D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000737:chemistry; D001665:Binding Sites; D002213:Capsid / Q000737:chemistry* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019696:Peptidylprolyl Isomerase; D011392:Proline / Q000737:chemistry; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014771:Virion / Q000737:chemistry
D002352:Carrier Proteins; D016655:HIV Core Protein p24; D001224:Aspartic Acid; D011392:Proline; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase