Fast folding of the two-domain semliki forest virus capsid protein explains co-translational proteolytic activity.
The capsid protein of Semliki Forest virus constitutes the N-terminal part of a large viral polyprotein. It consists of an unstructured basic segment (residues 1-118) and a 149 residue serine protease module (SFVP, residues 119-267) comprised of two beta-barrel domains. Previous in vivo and in vitro translation experiments have demonstrated that SFVP folds co-translationally during synthesis of the viral polyprotein and rapidly cleaves itself off the nascent chain. To test whether fast co-translation folding of SFVP is an intrinsic property of the polypeptide chain or whether folding is accelerated by cellular components, we investigated spontaneous folding of recombinant SFVP in vitro. The results show that the majority of unfolded SFVP molecules fold faster than any previously studied two-domain protein (tau=50 ms), and that folding of the N-terminal domain precedes structure formation of the C-terminal domain. This shows that co-translational folding of SFVP does not require additional cellular components and suggests that rapid folding is the result of molecular evolution towards efficient virus biogenesis.
Sánchez
Ignacio E
IE
Biozentrum der Universität Basel, Abteilung Biophysikalische Chemie, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
Morillas
Manuel
M
Zobeley
Eva
E
Kiefhaber
Thomas
T
Glockshuber
Rudi
R
D002213:Capsid / Q000737:chemistry*; D036022:Capsid Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010447:Peptide Hydrolases / Q000378:metabolism*; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012672:Semliki forest virus / Q000737:chemistry*
D036022:Capsid Proteins; D011994:Recombinant Proteins; D010447:Peptide Hydrolases