Co-translational folding of an alphavirus capsid protein in the cytosol of living cells.
The Semliki Forest virus capsid protein contains a chymotrypsin-like protease domain that must fold before it can autocatalytically cleave the protein from a larger polyprotein precursor. Here we analyse this cleavage in living mammalian and prokaryotic cells, and find that it occurs immediately after the emergence of the protease domain from the ribosome during protein synthesis. The acquisition of the native conformation of this domain thus occurs rapidly and at the same time as translation. It does not require termination of translation or release from the ribosome, and nor does it involve Hsp70 binding. These results provide direct evidence that protein folding can occur co-translationally in the cytosol of both prokaryotes and eukaryotes.
Nicola
A V
AV
Swiss Federal Institute of Technology, Institute of Biochemistry, Universitätstrasse 16, CH-8092 Zurich, Switzerland.
Chen
W
W
Helenius
A
A
D000818:Animals; D016466:CHO Cells; D002213:Capsid / Q000378:metabolism*; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D004926:Escherichia coli; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D010443:Peptide Chain Termination, Translational; D014176:Protein Biosynthesis; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D012672:Semliki forest virus / Q000378:metabolism*
D018840:HSP70 Heat-Shock Proteins