Structural investigation and kinetic characterization of potential cleavage sites of HIV GP160 by human furin and PC1.
A key event in the biosynthesis of the human immunodeficiency virus is the maturation of the gp160 precursor generating gp120 and gp41, two proteins that are fundamental for the infective process. In vivo, gp160 is specifically cleaved at the 515-519 site (REKR decreases A), in spite of the presence in its sequence of another consensus sequence KAKR decreases R (residues 507-511). Comparative kinetic studies on synthetic peptides reproducing different sequences of gp160 by the enzymes PC1 and furin are reported in this paper. The data demonstrate the higher efficiency of furin in the cleavage of peptidic substrates with respect to PC1 and its preference for REKR decreases A vs. KAKR decreases R. Furthermore, furin and PC1 are unable to process peptides patterned on the sequence 307-330 of specific viral strains of the gp120 V3 loop.
Brakch
N
N
Institute of Industrial Chemistry, University of Padua, Italy.
Dettin
M
M
Scarinci
C
C
Seidah
N G
NG
Di Bello
C
C
D000595:Amino Acid Sequence; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D016384:Consensus Sequence; D045683:Furin; D015686:Gene Products, env / Q000737:chemistry / Q000378:metabolism*; D006678:HIV / Q000378:metabolism; D019302:HIV Envelope Protein gp160; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D043484:Proprotein Convertases; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity; D013381:Subtilisins / Q000378:metabolism*
D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D010455:Peptides; D011498:Protein Precursors; D043484:Proprotein Convertases; D013381:Subtilisins; D045683:Furin; D016282:Aspartic Acid Endopeptidases