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| | <StructureSection load='1i9w' size='340' side='right'caption='[[1i9w]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='1i9w' size='340' side='right'caption='[[1i9w]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1i9w]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Semliki_forest_virus Semliki forest virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I9W OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1I9W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1i9w]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Semliki_Forest_virus Semliki Forest virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I9W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1I9W FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1i9w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i9w OCA], [http://pdbe.org/1i9w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1i9w RCSB], [http://www.ebi.ac.uk/pdbsum/1i9w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1i9w ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1i9w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i9w OCA], [https://pdbe.org/1i9w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1i9w RCSB], [https://www.ebi.ac.uk/pdbsum/1i9w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1i9w ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/POLS_SFV POLS_SFV]] 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 clathrin-mediated endocytosis their membrane fuses with the host endosomal 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.<ref>PMID:1962454</ref> <ref>PMID:1433520</ref> <ref>PMID:7983743</ref> <ref>PMID:15954801</ref> E3 protein's function is unknown.<ref>PMID:1962454</ref> <ref>PMID:1433520</ref> <ref>PMID:7983743</ref> <ref>PMID:15954801</ref> 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.<ref>PMID:1962454</ref> <ref>PMID:1433520</ref> <ref>PMID:7983743</ref> <ref>PMID:15954801</ref> 6K is a constitutive membrane protein involved in virus glycoprotein processing, cell permeabilization, and the budding of viral particles. Disrupts the calcium homeostasis of the cell, probably at the endoplasmic reticulum level. This leads to cytoplasmic calcium elevation. 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. Present in low amount in virions, about 3% compared to viral glycoproteins.<ref>PMID:1962454</ref> <ref>PMID:1433520</ref> <ref>PMID:7983743</ref> <ref>PMID:15954801</ref> 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 endosome and viral membrane fusion. Efficient fusion requires the presence of cholesterol and sphingolipid in the target membrane. Fusion is optimal at levels of about 1 molecule of cholesterol per 2 molecules of phospholipids, and is specific for sterols containing a 3-beta-hydroxyl group.<ref>PMID:1962454</ref> <ref>PMID:1433520</ref> <ref>PMID:7983743</ref> <ref>PMID:15954801</ref> | + | [https://www.uniprot.org/uniprot/POLS_SFV POLS_SFV] 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 clathrin-mediated endocytosis their membrane fuses with the host endosomal 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.<ref>PMID:1962454</ref> <ref>PMID:1433520</ref> <ref>PMID:7983743</ref> <ref>PMID:15954801</ref> E3 protein's function is unknown.<ref>PMID:1962454</ref> <ref>PMID:1433520</ref> <ref>PMID:7983743</ref> <ref>PMID:15954801</ref> 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.<ref>PMID:1962454</ref> <ref>PMID:1433520</ref> <ref>PMID:7983743</ref> <ref>PMID:15954801</ref> 6K is a constitutive membrane protein involved in virus glycoprotein processing, cell permeabilization, and the budding of viral particles. Disrupts the calcium homeostasis of the cell, probably at the endoplasmic reticulum level. This leads to cytoplasmic calcium elevation. 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. Present in low amount in virions, about 3% compared to viral glycoproteins.<ref>PMID:1962454</ref> <ref>PMID:1433520</ref> <ref>PMID:7983743</ref> <ref>PMID:15954801</ref> 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 endosome and viral membrane fusion. Efficient fusion requires the presence of cholesterol and sphingolipid in the target membrane. Fusion is optimal at levels of about 1 molecule of cholesterol per 2 molecules of phospholipids, and is specific for sterols containing a 3-beta-hydroxyl group.<ref>PMID:1962454</ref> <ref>PMID:1433520</ref> <ref>PMID:7983743</ref> <ref>PMID:15954801</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 18: |
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| | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1i9w ConSurf]. | | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1i9w ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| - | <div style="background-color:#fffaf0;"> | |
| - | == Publication Abstract from PubMed == | |
| - | Semliki Forest virus (SFV) has been extensively studied as a model for analyzing entry of enveloped viruses into target cells. Here we describe the trace of the polypeptide chain of the SFV fusion glycoprotein, E1, derived from an electron density map at 3.5 A resolution and describe its interactions at the surface of the virus. E1 is unexpectedly similar to the flavivirus envelope protein, with three structural domains disposed in the same primary sequence arrangement. These results introduce a new class of membrane fusion proteins which display lateral interactions to induce the necessary curvature and direct budding of closed particles. The resulting surface protein lattice is primed to cause membrane fusion when exposed to the acidic environment of the endosome. | |
| - | | |
| - | The Fusion glycoprotein shell of Semliki Forest virus: an icosahedral assembly primed for fusogenic activation at endosomal pH.,Lescar J, Roussel A, Wien MW, Navaza J, Fuller SD, Wengler G, Wengler G, Rey FA Cell. 2001 Apr 6;105(1):137-48. PMID:11301009<ref>PMID:11301009</ref> | |
| - | | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | </div> | |
| - | <div class="pdbe-citations 1i9w" style="background-color:#fffaf0;"></div> | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Line 32: |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Semliki forest virus]] | + | [[Category: Semliki Forest virus]] |
| - | [[Category: Fuller, S D]] | + | [[Category: Fuller SD]] |
| - | [[Category: Lescar, J]] | + | [[Category: Lescar J]] |
| - | [[Category: Navaza, J]] | + | [[Category: Navaza J]] |
| - | [[Category: Rey, F A]] | + | [[Category: Rey FA]] |
| - | [[Category: Roussel, A]] | + | [[Category: Roussel A]] |
| - | [[Category: Wengler, G]] | + | [[Category: Wengler G]] |
| - | [[Category: Wien, M W]] | + | [[Category: Wien MW]] |
| - | [[Category: Envelope glycoprotein]]
| + | |
| - | [[Category: Membrane fusion]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| - | [[Category: Virus]]
| + | |
| Structural highlights
Function
POLS_SFV 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 clathrin-mediated endocytosis their membrane fuses with the host endosomal 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.[1] [2] [3] [4] E3 protein's function is unknown.[5] [6] [7] [8] 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.[9] [10] [11] [12] 6K is a constitutive membrane protein involved in virus glycoprotein processing, cell permeabilization, and the budding of viral particles. Disrupts the calcium homeostasis of the cell, probably at the endoplasmic reticulum level. This leads to cytoplasmic calcium elevation. 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. Present in low amount in virions, about 3% compared to viral glycoproteins.[13] [14] [15] [16] 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 endosome and viral membrane fusion. Efficient fusion requires the presence of cholesterol and sphingolipid in the target membrane. Fusion is optimal at levels of about 1 molecule of cholesterol per 2 molecules of phospholipids, and is specific for sterols containing a 3-beta-hydroxyl group.[17] [18] [19] [20]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Lusa S, Garoff H, Liljestrom P. Fate of the 6K membrane protein of Semliki Forest virus during virus assembly. Virology. 1991 Dec;185(2):843-6. PMID:1962454
- ↑ Wahlberg JM, Bron R, Wilschut J, Garoff H. Membrane fusion of Semliki Forest virus involves homotrimers of the fusion protein. J Virol. 1992 Dec;66(12):7309-18. PMID:1433520
- ↑ Loewy A, Smyth J, von Bonsdorff CH, Liljestrom P, Schlesinger MJ. The 6-kilodalton membrane protein of Semliki Forest virus is involved in the budding process. J Virol. 1995 Jan;69(1):469-75. PMID:7983743
- ↑ Vonderheit A, Helenius A. Rab7 associates with early endosomes to mediate sorting and transport of Semliki forest virus to late endosomes. PLoS Biol. 2005 Jul;3(7):e233. Epub 2005 Jun 21. PMID:15954801 doi:10.1371/journal.pbio.0030233
- ↑ Lusa S, Garoff H, Liljestrom P. Fate of the 6K membrane protein of Semliki Forest virus during virus assembly. Virology. 1991 Dec;185(2):843-6. PMID:1962454
- ↑ Wahlberg JM, Bron R, Wilschut J, Garoff H. Membrane fusion of Semliki Forest virus involves homotrimers of the fusion protein. J Virol. 1992 Dec;66(12):7309-18. PMID:1433520
- ↑ Loewy A, Smyth J, von Bonsdorff CH, Liljestrom P, Schlesinger MJ. The 6-kilodalton membrane protein of Semliki Forest virus is involved in the budding process. J Virol. 1995 Jan;69(1):469-75. PMID:7983743
- ↑ Vonderheit A, Helenius A. Rab7 associates with early endosomes to mediate sorting and transport of Semliki forest virus to late endosomes. PLoS Biol. 2005 Jul;3(7):e233. Epub 2005 Jun 21. PMID:15954801 doi:10.1371/journal.pbio.0030233
- ↑ Lusa S, Garoff H, Liljestrom P. Fate of the 6K membrane protein of Semliki Forest virus during virus assembly. Virology. 1991 Dec;185(2):843-6. PMID:1962454
- ↑ Wahlberg JM, Bron R, Wilschut J, Garoff H. Membrane fusion of Semliki Forest virus involves homotrimers of the fusion protein. J Virol. 1992 Dec;66(12):7309-18. PMID:1433520
- ↑ Loewy A, Smyth J, von Bonsdorff CH, Liljestrom P, Schlesinger MJ. The 6-kilodalton membrane protein of Semliki Forest virus is involved in the budding process. J Virol. 1995 Jan;69(1):469-75. PMID:7983743
- ↑ Vonderheit A, Helenius A. Rab7 associates with early endosomes to mediate sorting and transport of Semliki forest virus to late endosomes. PLoS Biol. 2005 Jul;3(7):e233. Epub 2005 Jun 21. PMID:15954801 doi:10.1371/journal.pbio.0030233
- ↑ Lusa S, Garoff H, Liljestrom P. Fate of the 6K membrane protein of Semliki Forest virus during virus assembly. Virology. 1991 Dec;185(2):843-6. PMID:1962454
- ↑ Wahlberg JM, Bron R, Wilschut J, Garoff H. Membrane fusion of Semliki Forest virus involves homotrimers of the fusion protein. J Virol. 1992 Dec;66(12):7309-18. PMID:1433520
- ↑ Loewy A, Smyth J, von Bonsdorff CH, Liljestrom P, Schlesinger MJ. The 6-kilodalton membrane protein of Semliki Forest virus is involved in the budding process. J Virol. 1995 Jan;69(1):469-75. PMID:7983743
- ↑ Vonderheit A, Helenius A. Rab7 associates with early endosomes to mediate sorting and transport of Semliki forest virus to late endosomes. PLoS Biol. 2005 Jul;3(7):e233. Epub 2005 Jun 21. PMID:15954801 doi:10.1371/journal.pbio.0030233
- ↑ Lusa S, Garoff H, Liljestrom P. Fate of the 6K membrane protein of Semliki Forest virus during virus assembly. Virology. 1991 Dec;185(2):843-6. PMID:1962454
- ↑ Wahlberg JM, Bron R, Wilschut J, Garoff H. Membrane fusion of Semliki Forest virus involves homotrimers of the fusion protein. J Virol. 1992 Dec;66(12):7309-18. PMID:1433520
- ↑ Loewy A, Smyth J, von Bonsdorff CH, Liljestrom P, Schlesinger MJ. The 6-kilodalton membrane protein of Semliki Forest virus is involved in the budding process. J Virol. 1995 Jan;69(1):469-75. PMID:7983743
- ↑ Vonderheit A, Helenius A. Rab7 associates with early endosomes to mediate sorting and transport of Semliki forest virus to late endosomes. PLoS Biol. 2005 Jul;3(7):e233. Epub 2005 Jun 21. PMID:15954801 doi:10.1371/journal.pbio.0030233
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