Cdc48 can distinguish between native and non-native proteins in the absence of cofactors.
The ATPase Cdc48 is required for membrane fusion and protein degradation. Recently it has been suggested that Cdc48 in a complex with Ufd1 and Npl4 acts as an ubiquitin-dependent chaperone. Here it is shown that recombinant Cdc48 alone can distinguish between the native and the non-native conformation of model substrates. First, Cdc48 prevents luciferase from aggregating following a heat shock. Second, it inhibits the aggregation of rhodanese upon dilution. Third, Cdc48 binds specifically to heat-denatured luciferase. These chaperone-like functions seem to be independent of ATPase activity. Furthermore, Cdc48 can act as a co-chaperone in the Hsc70-Hsp40 chaperone system. These results show that Cdc48 possesses chaperone-like activities and can functionally interact with Hsc70. Cdc48's ability to recognise denatured proteins can also be a source of unspecific binding in biochemical interaction experiments.
Thoms
Sven
S
ZMBH, Center for Molecular Biology, Heidelberg University, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany. s.thoms@zmbh.uni-heidelberg.de
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000251:Adenosine Triphosphatases; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D015870:Gene Expression; D050883:HSC70 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006358:Hot Temperature; D008156:Luciferases / Q000737:chemistry / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011489:Protein Denaturation / Q000187:drug effects; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D013884:Thiosulfate Sulfurtransferase / Q000737:chemistry; D000074405:Valosin Containing Protein
D018797:Cell Cycle Proteins; D050883:HSC70 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D011506:Proteins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D008156:Luciferases; D013884:Thiosulfate Sulfurtransferase; D000251:Adenosine Triphosphatases; D000074405:Valosin Containing Protein