Role of the C-terminal tryptophan residue for the structure-function of the alphavirus capsid protein

Journal of Molecular Biology
U Skoging, P Liljeström

Abstract

The Semliki Forest virus capsid protein is a multifunctional protein which packages genomic RNA into nucleocapsid structures and binds to viral spike protein during budding. In addition, the capsid protein has an autoproteolytic activity whereby the C-terminal tryptophan is used as the substrate for cotranslational cleavage of the viral structure polyprotein. The autoproteolytic domain of the capsid protein has a chymotrypsin-like fold but has two additional short beta-strands which place the tryptophan into the active site. Here, we have substituted the C-terminal tryptophan of Semliki Forest virus capsid protein for alanine, arginine and phenylalanine and analysed the effects on different functions of the C protein such as nucleocapsid formation, spike binding and autoproteolytic activity. We found that (i) tryptophan is a better substrate for the autoproteolytic activity, (ii) the wild-type tryptophan is the only residue that allows efficient viral growth and (iii) an aromatic residue is important for correct initial folding and stability of the protein.

References

Dec 1, 1977·Journal of Virology·H Söderlund, I Ulmanen
Mar 6, 1992·Science·L HedstromW J Rutter
Aug 1, 1992·Journal of Virology·M SuomalainenH Garoff
Dec 1, 1989·Journal of Virology·B WeissS Schlesinger
Jan 1, 1987·Methods in Enzymology·T A KunkelR A Zakour
Aug 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·C S HahnJ H Strauss
Apr 20, 1995·Virology·T RümenapfJ H Strauss
Mar 1, 1995·Protein Science : a Publication of the Protein Society·J J Perona, C S Craik
Mar 1, 1993·Journal of Virology·U Geigenmüller-GnirkeS Schlesinger
May 10, 1996·Journal of Molecular Biology·A M Lesk, W D Fordham
Sep 20, 1996·Journal of Molecular Biology·H K ChoiR J Kuhn
Mar 1, 1997·Proteins·H K ChoiM G Rossmann

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Citations

Apr 20, 2001·Journal of Virology·U Skoging-Nyberg, P Liljeström
Jan 9, 1999·Journal of Virology·C Smerdou, P Liljeström
Feb 28, 2021·Molecular Microbiology·Joshua S MacCreadyAnthony G Vecchiarelli
May 13, 2021·MBio·Joshua S MacCready, Anthony G Vecchiarelli
Dec 14, 2005·Journal of Molecular Biology·Alfredo CastellóLuis Carrasco
Jan 8, 2008·Journal of Molecular Biology·Manuel MorillasEva Kuennemann
Dec 12, 2002·Chemical Reviews·Liang Tong

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