Structural investigation of the HIV-1 envelope glycoprotein gp160 cleavage site, 2: relevance of an N-terminal helix(464 views) Oliva R, Falcigno L, D'Auria G, Dettin M, Scarinci C, Pasquato A, Di Bello C, Paolillo L
Chembiochem (ISSN: 1439-4227, 1439-7633, 1439-7633electronic), 2003 Aug 4; 4(8): 727-733.
Keywords: Conformation Analysis, Gp160, Hiv, Molecular Modeling, Nmr Spectroscopy, Glycoprotein Gp 160, Virus Glycoprotein, Article, Enzyme Activity, Human Immunodeficiency Virus, Nonhuman, Nuclear Magnetic Resonance Spectroscopy, Priority Journal, Protein Conformation, Protein Degradation, Protein Structure, Virus Envelope, Amino Acid Sequence, Catalytic Domain, Circular Dichroism, Consensus Sequence, Furin, Hiv Envelope Protein Gp160, Hiv Infections, Molecular Sequence Data, Biomolecular, Peptide Fragments, Sequence Homology, Subtilisins, Hiv Envelope Protein Gp160 Chemistry Metabolism, Hiv Infections Metabolism Virology, Hiv-1 Chemistry, Peptide Fragments Chemistry, Subtilisins Chemistry Metabolism,
Affiliations: *** IBB - CNR ***
Dipartimento di Chimica, Universita di Napoli Federico II, Complesso Univ. Monte S. Angelo, Via Cintia, 80126 Napoli, Italy
Ist. Biostrutture/Bioimmagini C. N. R., Universita di Napoli Federico II, Via Mezzocannone 4, 80134 Napoli, Italy
Dipto. Proc. Chimici dell'Ingegneria, Universit di Padova, Via Marzolo 9, 35131 Padova, Italy
References: Not available.
Structural investigation of the HIV-1 envelope glycoprotein gp160 cleavage site, 2: relevance of an N-terminal helix
Proteolytic activation of the HIV-1 envelope glycoprotein gp160 is selectively performed by the proprotein convertase furin at the C-terminus of the sequence R508-E-K-R511 (site 1), in spite of the presence of another consensus sequence, Lys500-Ala-Lys-Arg503 (site 2). On the basis of the solution structural analysis of the synthetic peptide p498, spanning the gp160 sequence Pro498-Gly516, we previously suggested a possible role of an N-terminal helix in regulating the exposure and accessibility of the gp160 physiological cleavage site, enclosed in a loop. Here we report on the activity and conformation of the 23-residue peptide h-REKR, designed to exhibit a large N-terminal helix, followed by the gp160 native sequence, Arg508-Gly516. h-REKR is digested by furin with high efficiency, comparable to the full native p498. Circular dichroism analyses, in mixtures from pure water to 98 % trifluoroethanol, outline a significant content of helical structure in the peptide conformation. The molecular model obtained from NMR data collected in trifluoroethanol/water, by means of DYANA and AMBER simulations, indeed has helical structure on a large N-terminal segment. Such a long helix does not seem to affect the loop conformation of the C-terminal site 1-containing sequence, which exhibits the same proton chemical shifts already observed for the full native p498.
Structural investigation of the HIV-1 envelope glycoprotein gp160 cleavage site, 2: relevance of an N-terminal helix