Inherent chaperone-like activity of aspartic proteases reveals a distant evolutionary relation to double-psi barrel domains of AAA-ATPases.
Chaperones and proteases share the ability to interact with unfolded proteins. Here we show that enzymatically inactive forms of the aspartic proteases HIV-1 protease and pepsin have inherent chaperone-like activity and can prevent the aggregation of denatured substrate proteins. In contrast to proteolysis, which requires dimeric enzymes, chaperone-like activity could be observed also with monomeric domains. The involvement of the active site cleft in the chaperone-like function was demonstrated by the inhibitory effect of peptide substrate inhibitors. The high structural similarity between aspartic proteases and the N-terminal double-psi barrels of Cdc48-like proteins, which are involved in the unfolding and dissociation of proteins, suggests that they share a common ancestor. The latent chaperone-like activity in aspartic proteases can be seen as a relic that has further evolved to serve substrate binding in the context of proteolytic activity.
Hulko
Michael
M
Department of Protein Evolution, Max-Planck-Institute for Developmental Biology, D-72076 Tübingen, Germany.
Lupas
Andrei N
AN
Martin
Jörg
J
D005075:Biological Evolution; D016333:HIV Protease / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism*; D010434:Pepsin A / Q000378:metabolism*; D011489:Protein Denaturation; D013820:Thermolysin / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism
D018832:Molecular Chaperones; D014357:Trypsin; D016333:HIV Protease; D010434:Pepsin A; D013820:Thermolysin