tailieunhanh - Báo cáo Y học: Solution structure of the HIV gp120 C5 Domain

InHIV the viral envelope protein is processed by a host cell protease gp120 are thought to directly interact with gp41 but are largely missing from the available X-ray structure. Bio-physical studies of theHIVgp120C5 domain (residues 489– 511 of HIV-1 strain HXB2), which corresponds to the carboxy terminal region of gp120, have been undertaken. | Eur. J. Biochem. 269 4860-4867 2002 FEBS 2002 doi Solution structure of the HIV gp120 C5 Domain Laure Guilhaudis Amy Jacobs and Michael Caffrey Department of Biochemistry and Molecular Biology University of Illinois at Chicago IL USA In HIV the viral envelope protein is processed by a host cell protease to form gp120 and gp41. TheC1 andC5 domains of gp120 are thought to directly interact with gp41 but are largely missing from the available X-ray structure. Biophysical studies of the HIV gp120 C5 domain residues 489511 of HIV-1 strain HXB2 which corresponds to the carboxy terminal region of gp120 have been undertaken. CD studies of the C5 domain suggest that it is unstructured in aqueous solutions but partially helical in trifluoroethanol aqueous and hexafluoroisopropanol aqueous buffers. The solution structure of the C5 peptide in 40 trifluoroethanol aqueous buffer was determined by NMR spectroscopy. The resulting structure is a turn helix structural motif consistent with the CD results. Fluorescence titration experiments suggest that HIV C5 forms a 1 1 complex with the HIV gp41 ectodomain in the presence of cosolvent with an apparent Kd of w M. The absence of complex formation in the absence of cosolvent indicates that formation of the turn-helix structural motif of C5 is necessary for complex formation. Examination of the C5 structure provides insight into the interaction between gp120 and gp41 and provides a possible target site for future drug therapies designed to disrupt the gp120 gp41 complex. In addition the C5 structure lends insight into the site of HIV envelope protein maturation by the host enzymes furin and PC7 which provides other possible targets for drug therapies. Keywords AIDS gp41 gp120 HIV NMR. Envelope proteins are known to play roles in directing viral particles to the appropriate target cell and initiating the fusion of the viral and cellular membranes in diverse viruses including retroviridae .

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