Non-viral cellular substrates for human immunodeficiency virus type 1 protease.
A computer search revealed 10 proteins with homology to the sequence we originally identified in vimentin as the site of cleavage by human immunodeficiency virus type 1 (HIV-1) protease. Of these 10 proteins (actin, alpha-actinin, spectrin, tropomyosins, vinculin, dystrophin, MAP-2, villin, TRK-1 and Ig mu-chain), we show that 4 of the first 5 were cleaved in vitro by this protease, as are MAP-1 and -2 [(1990) J. Gen. Virol. 71, 1985-1991]. In these proteins, cleavage is not restricted to a single motif, but occurs at many sites. However, cleavage is not random, since 9 other proteins including the cytoskeletal proteins filamin and band 4.1 are not cleaved in the in vitro assay. Thus, the ability of HIV-1 protease to cleave specific components of the cytoskeleton may be an important, although as yet unevaluated aspect of the life cycle of this retrovirus and/or may directly contribute to the pathogenesis observed during infection.
Shoeman
R L
RL
Max-Planck-Institut für Zellbiologie, Ladenburg/Heidelberg, Germany.
Kesselmier
C
C
Mothes
E
E
Höner
B
B
Traub
P
P
D000595:Amino Acid Sequence; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D016189:Dystrophin / Q000378:metabolism*; D016333:HIV Protease / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D003598:Cytoskeletal Proteins; D016189:Dystrophin; D007136:Immunoglobulins; D016333:HIV Protease