10         20         30         40         50         60
         |          |          |          |          |          |
MNRGFFNMLG RRPFPAPTAM WRPRRRRQAA PMPARNGLAS QIQQLTTAVS ALVIGQATRP - 60
QNPRPRPPPR QKKQAPKQPP KPKKPKPQEK KKKQPAKTKP GKRQRMALKL EADRLFDVKN - 120
EDGDVIGHAL AMEGKVMKPL HVKGTIDHPV LSKLKFTKSS AYDMEFAQLP VNMRSEAFTY - 180
TSEHPEGFYN WHHGAVQYSG GRFTIPRGVG GRGDSGRPIM DNSGRVVAIV LGGADEGTRT - 240
ALSVVTWNSK GKTIKTTPEG TEEWSAAPLV TAMCLLGNVS FPCNRPPTCY TREPSRALDI - 300
LEENVNHEAY DTLLNAILRC GSSGRSKRSV TDDFTLTSPY LGTCSYCHHT EPCFSPIKIE - 360
QVWDEADDNT IRIQTSAQFG YDKSGAASTN KYRYMSFEQD HTVKEGTMDD IKISTSGPCR - 420
RLSYKGYFLL AKCPPGDSVT VSIASSNSAT SCTMARKIKP KFVGREKYDL PPVHGKKIPC - 480
TVYDRLKETT AGYITMHRPG PHAYTSYLEE SSGKVYAKPP SGKNITYECK CGDYKTGTVT - 540
TRTEITGCTA IKQCVAYKSD QTKWVFNSPD LIRHADHTAQ GKLHLPFKLI PSTCMVPVAH - 600
APNVIHGFKH ISLQLDTDHL TLLTTRRLGA NPEPTTEWII GKTVRNFTVD RDGLEYIWGN - 660
HEPVRVYAQE SAPGDPHGWP HEIVQHYYHR HPVYTILAVA SAAVAMMIGV TVAALCACKA - 720
RRECLTPYAL APNAVIPTSL ALLCCVRSAN AETFTETMSY FWSNSQPFFW VQLCIPLAAV - 780
IVLMRCCSCC LPFLVVAGAY LAKVDAYEHA TTVPNVPQIP YKALVERAGY APLNLEITVM - 840
SSEVLPSTNQ EYITCKFTTV VPSPKVKCCG SLECQPAAHA DYTCKVFGGV YPFMWGGAQC - 900
FCDSENSQMS EAYVELSADC ATDHAQAIKV HTAAMKVGLR IVYGNTTSFL DVYVNGVTPG - 960
TSKDLKVIAG PISASFTPFD HKVVIHRGLV YNYDFPEYGA MKPGVFGDIQ ATSLTSKDLI - 1020
ASTDIRLLKP SAKNVHVPYT QAASGFEMWK NNSGRPLQET APFGCKIAVN PLRAVDCSYG - 1080
NIPISIDIPN AAFIRTSDAP LVSTVKCDVS ECTYSADFGG MATLQYVSDR EGQCPVHSHS - 1140
STATLQESTV HVLEKGAVTV HFSTASPQAN FIVSLCGKKT TCNAECKPPA DHIVSTPHKN - 1200
DQEFQAAISK TSWSWLFALF GGASSLLIIG LTIFACSMML TSTRR

Capsid protein possesses a protease activity that results in its autocatalytic cleavage from the nascent structural protein. Following its self-cleavage, the capsid protein transiently associates with ribosomes, and within several minutes the protein binds to viral RNA and rapidly assembles into icosaedric core particles. The resulting nucleocapsid eventually associates with the cytoplasmic domain of E2 at the cell membrane, leading to budding and formation of mature virions. New virions attach to target cells, and after endocytosis their membrane fuses with the target cell membrane. This leads to the release of the nucleocapsid into the cytoplasm, followed by an uncoating event necessary for the genomic RNA to become accessible. The uncoating might be triggered by the interaction of capsid proteins with ribosomes. Binding of ribosomes would release the genomic RNA since the same region is genomic RNA-binding and ribosome-binding. E3 protein's function is unknown. E2 is responsible for viral attachment to target host cell, by binding to the cell receptor. Synthesized as a p62 precursor which is processed by furin at the cell membrane just before virion budding, giving rise to E2-E1 heterodimer. The p62-E1 heterodimer is stable, whereas E2-E1 is unstable and dissociate at low pH. p62 is processed at the last step, presumably to avoid E1 fusion activation before its final export to cell surface. E2 C-terminus contains a transitory transmembrane that would be disrupted by palmitoylation, resulting in reorientation of the C-terminal tail from lumenal to cytoplasmic side. This step is critical since E2 C-terminus is involved in budding by interacting with capsid proteins. This release of E2 C-terminus in cytoplasm occurs lately in protein export, and precludes premature assembly of particles at the endoplasmic reticulum membrane. 6K is a constitutive membrane protein involved in virus glycoprotein processing, membrane permeabilization, and the budding of viral particles. Because of its lipophilic properties, the 6K protein is postulated to influence the selection of lipids that interact with the transmembrane domains of the glycoproteins, which, in turn, affects the deformability of the bilayer required for the extreme curvature that occurs as budding proceeds. E1 is a class II viral fusion protein. Fusion activity is inactive as long as E1 is bound to E2 in mature virion. After virus attachment to target cell and endocytosis, acidification of the endosome would induce dissociation of E1/E2 heterodimer and concomitant trimerization of the E1 subunits. This E1 trimer is fusion active, and promotes release of viral nucleocapsid in cytoplasm after cell and viral membrane fusion. Efficient fusion requires the presence of cholesterol and sphingolipid in the target membrane.

1. Choi HK, Lee S, Zhang YP, McKinney BR, Wengler G, Rossmann MG, Kuhn RJ. "Structural analysis of Sindbis virus capsid mutants involving assembly and catalysis." J Mol Biol. 1996; 262(2): 151-167. PubMed: 8831786
   
   

Previous entry DP00066 has been split into polyprotein DP00066 and cleavage product DP00066_C001. Disorder is characterized on the cleavage product.