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Structural Investigation of the HIV‐1 Envelope Glycoprotein gp160 Cleavage Site, 2: Relevance of an N‐Terminal Helix
Author(s) -
Oliva Romina,
Falcigno Lucia,
D′Auria Gabriella,
Dettin Monica,
Scarinci Claudia,
Pasquato Antonella,
Di Bello Carlo,
Paolillo Livio
Publication year - 2003
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200200541
Subject(s) - furin , chemistry , circular dichroism , peptide , cleavage (geology) , stereochemistry , helix (gastropod) , protein structure , peptide sequence , protein secondary structure , biochemistry , enzyme , biology , paleontology , ecology , fracture (geology) , snail , gene
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.