5drv: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older editNewer edit →
m Protected "5drv" [edit=sysop:move=sysop]
No edit summary
Line 1: Line 1:
'''Unreleased structure'''
==Crystal structure of the G3BP2 NTF2-like domain in complex with a peptide==
<StructureSection load='5drv' size='340' side='right' caption='[[5drv]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5drv]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DRV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DRV FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fcj|4fcj]], [[4fcm|4fcm]], [[3q90|3q90]], [[4iia|4iia]]</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5drv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5drv OCA], [http://pdbe.org/5drv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5drv RCSB], [http://www.ebi.ac.uk/pdbsum/5drv PDBsum]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/G3BP2_HUMAN G3BP2_HUMAN]] Probable scaffold protein that may be involved in mRNA transport. [[http://www.uniprot.org/uniprot/POLN_SFV POLN_SFV]] P123 is short-lived polyproteins, accumulating during early stage of infection. It localizes the viral replication complex to the cytoplasmic surface of modified endosomes and lysosomes. By interacting with nsP4, it starts viral genome replication into antigenome. After these early events, P123 is cleaved sequentially into nsP1, nsP2 and nsP3. This sequence of delayed processing would allow correct assembly and membrane association of the RNA polymerase complex.<ref>PMID:8057461</ref> <ref>PMID:7831320</ref> <ref>PMID:8985362</ref> <ref>PMID:9811773</ref> <ref>PMID:10217401</ref> <ref>PMID:10748213</ref> <ref>PMID:16352561</ref> <ref>PMID:22514352</ref>  nsP1 is a cytoplasmic capping enzyme. This function is necessary since all viral RNAs are synthesized in the cytoplasm, and host capping enzymes are restricted to the nucleus. The enzymatic reaction involves a covalent link between 7-methyl-GMP and nsP1, whereas eukaryotic capping enzymes form a covalent complex only with GMP. nsP1 capping would consist in the following reactions: GTP is first methylated and then forms the m7GMp-nsP1 complex, from which 7-methyl-GMP complex is transferred to the mRNA to create the cap structure. Palmitoylated nsP1 is remodeling host cell cytoskeleton, and induces filopodium-like structure formation at the surface of the host cell.<ref>PMID:8057461</ref> <ref>PMID:7831320</ref> <ref>PMID:8985362</ref> <ref>PMID:9811773</ref> <ref>PMID:10217401</ref> <ref>PMID:10748213</ref> <ref>PMID:16352561</ref> <ref>PMID:22514352</ref>  nsP2 has two separate domain with different biological activities. The N-terminal section is part of the RNA polymerase complex and has RNA trisphosphatase and RNA helicase activity. The C-terminal section harbors a protease that specifically cleaves and releases the four mature proteins. Also inhibits cellular transcription by inducing rapid degradation of POLR2A, a catalytic subunit of the RNAPII complex. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response.<ref>PMID:8057461</ref> <ref>PMID:7831320</ref> <ref>PMID:8985362</ref> <ref>PMID:9811773</ref> <ref>PMID:10217401</ref> <ref>PMID:10748213</ref> <ref>PMID:16352561</ref> <ref>PMID:22514352</ref>  nsP3 is essential for minus strand and subgenomic 26S mRNA synthesis.<ref>PMID:8057461</ref> <ref>PMID:7831320</ref> <ref>PMID:8985362</ref> <ref>PMID:9811773</ref> <ref>PMID:10217401</ref> <ref>PMID:10748213</ref> <ref>PMID:16352561</ref> <ref>PMID:22514352</ref>  nsP4 is an RNA dependent RNA polymerase. It replicates genomic and antigenomic RNA by recognizing replications specific signals. Transcribes also a 26S subgenomic mRNA by initiating RNA synthesis internally on antigenomic RNA. This 26S mRNA codes for structural proteins.<ref>PMID:8057461</ref> <ref>PMID:7831320</ref> <ref>PMID:8985362</ref> <ref>PMID:9811773</ref> <ref>PMID:10217401</ref> <ref>PMID:10748213</ref> <ref>PMID:16352561</ref> <ref>PMID:22514352</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The crystal structure of the NTF2-like domain of the human Ras GTPase SH3 Binding Protein (G3BP), isoform 2, was determined at a resolution of 2.75 A in complex with a peptide containing a FGDF sequence motif. The overall structure of the protein is highly similar to the homodimeric N-terminal domains of the G3BP1 and Rasputin proteins. Recently, a subset of G3BP interacting proteins was recognized to share a common sequence motif, FGDF. The most studied binding partners, USP10 and viral nsP3, interfere with essential G3BP functions related to assembly of cellular stress granules. Reported molecular modeling suggested that FGDF-motif containing peptides bind in an extended conformation into a hydrophobic groove on the surface of the G3BP NTF2-like domain in a manner similar to the known binding of FxFG nucleoporin repeats. The results in this paper provide evidence for a different binding mode. The FGDF peptide binds and changes conformation of the protruding N-terminal residues by providing hydrophobic interactions to a symmetry related molecule that facilitated crystallization of the G3BP2 isoform.


The entry 5drv is ON HOLD  until Paper Publication
Crystal structure of the G3BP2 NTF2-like domain in complex with a canonical FGDF motif peptide.,Kristensen O Biochem Biophys Res Commun. 2015 Sep 26. pii: S0006-291X(15)30640-9. doi:, 10.1016/j.bbrc.2015.09.123. PMID:26410532<ref>PMID:26410532</ref>


Authors: Kristensen, O.
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
Description:  
<div class="pdbe-citations 5drv" style="background-color:#fffaf0;"></div>
[[Category: Unreleased Structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Kristensen, O]]
[[Category: Kristensen, O]]
[[Category: G3bp]]
[[Category: Ntf2-like]]
[[Category: Peptide complex]]
[[Category: Protein binding]]

Revision as of 06:55, 16 October 2015

Crystal structure of the G3BP2 NTF2-like domain in complex with a peptideCrystal structure of the G3BP2 NTF2-like domain in complex with a peptide

Structural highlights

5drv is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[G3BP2_HUMAN] Probable scaffold protein that may be involved in mRNA transport. [POLN_SFV] P123 is short-lived polyproteins, accumulating during early stage of infection. It localizes the viral replication complex to the cytoplasmic surface of modified endosomes and lysosomes. By interacting with nsP4, it starts viral genome replication into antigenome. After these early events, P123 is cleaved sequentially into nsP1, nsP2 and nsP3. This sequence of delayed processing would allow correct assembly and membrane association of the RNA polymerase complex.[1] [2] [3] [4] [5] [6] [7] [8] nsP1 is a cytoplasmic capping enzyme. This function is necessary since all viral RNAs are synthesized in the cytoplasm, and host capping enzymes are restricted to the nucleus. The enzymatic reaction involves a covalent link between 7-methyl-GMP and nsP1, whereas eukaryotic capping enzymes form a covalent complex only with GMP. nsP1 capping would consist in the following reactions: GTP is first methylated and then forms the m7GMp-nsP1 complex, from which 7-methyl-GMP complex is transferred to the mRNA to create the cap structure. Palmitoylated nsP1 is remodeling host cell cytoskeleton, and induces filopodium-like structure formation at the surface of the host cell.[9] [10] [11] [12] [13] [14] [15] [16] nsP2 has two separate domain with different biological activities. The N-terminal section is part of the RNA polymerase complex and has RNA trisphosphatase and RNA helicase activity. The C-terminal section harbors a protease that specifically cleaves and releases the four mature proteins. Also inhibits cellular transcription by inducing rapid degradation of POLR2A, a catalytic subunit of the RNAPII complex. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response.[17] [18] [19] [20] [21] [22] [23] [24] nsP3 is essential for minus strand and subgenomic 26S mRNA synthesis.[25] [26] [27] [28] [29] [30] [31] [32] nsP4 is an RNA dependent RNA polymerase. It replicates genomic and antigenomic RNA by recognizing replications specific signals. Transcribes also a 26S subgenomic mRNA by initiating RNA synthesis internally on antigenomic RNA. This 26S mRNA codes for structural proteins.[33] [34] [35] [36] [37] [38] [39] [40]

Publication Abstract from PubMed

The crystal structure of the NTF2-like domain of the human Ras GTPase SH3 Binding Protein (G3BP), isoform 2, was determined at a resolution of 2.75 A in complex with a peptide containing a FGDF sequence motif. The overall structure of the protein is highly similar to the homodimeric N-terminal domains of the G3BP1 and Rasputin proteins. Recently, a subset of G3BP interacting proteins was recognized to share a common sequence motif, FGDF. The most studied binding partners, USP10 and viral nsP3, interfere with essential G3BP functions related to assembly of cellular stress granules. Reported molecular modeling suggested that FGDF-motif containing peptides bind in an extended conformation into a hydrophobic groove on the surface of the G3BP NTF2-like domain in a manner similar to the known binding of FxFG nucleoporin repeats. The results in this paper provide evidence for a different binding mode. The FGDF peptide binds and changes conformation of the protruding N-terminal residues by providing hydrophobic interactions to a symmetry related molecule that facilitated crystallization of the G3BP2 isoform.

Crystal structure of the G3BP2 NTF2-like domain in complex with a canonical FGDF motif peptide.,Kristensen O Biochem Biophys Res Commun. 2015 Sep 26. pii: S0006-291X(15)30640-9. doi:, 10.1016/j.bbrc.2015.09.123. PMID:26410532[41]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Rikkonen M, Peranen J, Kaariainen L. ATPase and GTPase activities associated with Semliki Forest virus nonstructural protein nsP2. J Virol. 1994 Sep;68(9):5804-10. PMID:8057461
  2. ↑ Ahola T, Kaariainen L. Reaction in alphavirus mRNA capping: formation of a covalent complex of nonstructural protein nsP1 with 7-methyl-GMP. Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):507-11. PMID:7831320
  3. ↑ Ahola T, Laakkonen P, Vihinen H, Kaariainen L. Critical residues of Semliki Forest virus RNA capping enzyme involved in methyltransferase and guanylyltransferase-like activities. J Virol. 1997 Jan;71(1):392-7. PMID:8985362
  4. ↑ Laakkonen P, Auvinen P, Kujala P, Kaariainen L. Alphavirus replicase protein NSP1 induces filopodia and rearrangement of actin filaments. J Virol. 1998 Dec;72(12):10265-9. PMID:9811773
  5. ↑ Gomez de Cedron M, Ehsani N, Mikkola ML, Garcia JA, Kaariainen L. RNA helicase activity of Semliki Forest virus replicase protein NSP2. FEBS Lett. 1999 Apr 1;448(1):19-22. PMID:10217401
  6. ↑ Vasiljeva L, Merits A, Auvinen P, Kaariainen L. Identification of a novel function of the alphavirus capping apparatus. RNA 5'-triphosphatase activity of Nsp2. J Biol Chem. 2000 Jun 9;275(23):17281-7. PMID:10748213 doi:http://dx.doi.org/10.1074/jbc.M910340199
  7. ↑ Sawicki DL, Perri S, Polo JM, Sawicki SG. Role for nsP2 proteins in the cessation of alphavirus minus-strand synthesis by host cells. J Virol. 2006 Jan;80(1):360-71. PMID:16352561 doi:http://dx.doi.org/10.1128/JVI.80.1.360-371.2006
  8. ↑ Akhrymuk I, Kulemzin SV, Frolova EI. Evasion of the innate immune response: the Old World alphavirus nsP2 protein induces rapid degradation of Rpb1, a catalytic subunit of RNA polymerase II. J Virol. 2012 Jul;86(13):7180-91. doi: 10.1128/JVI.00541-12. Epub 2012 Apr 18. PMID:22514352 doi:http://dx.doi.org/10.1128/JVI.00541-12
  9. ↑ Rikkonen M, Peranen J, Kaariainen L. ATPase and GTPase activities associated with Semliki Forest virus nonstructural protein nsP2. J Virol. 1994 Sep;68(9):5804-10. PMID:8057461
  10. ↑ Ahola T, Kaariainen L. Reaction in alphavirus mRNA capping: formation of a covalent complex of nonstructural protein nsP1 with 7-methyl-GMP. Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):507-11. PMID:7831320
  11. ↑ Ahola T, Laakkonen P, Vihinen H, Kaariainen L. Critical residues of Semliki Forest virus RNA capping enzyme involved in methyltransferase and guanylyltransferase-like activities. J Virol. 1997 Jan;71(1):392-7. PMID:8985362
  12. ↑ Laakkonen P, Auvinen P, Kujala P, Kaariainen L. Alphavirus replicase protein NSP1 induces filopodia and rearrangement of actin filaments. J Virol. 1998 Dec;72(12):10265-9. PMID:9811773
  13. ↑ Gomez de Cedron M, Ehsani N, Mikkola ML, Garcia JA, Kaariainen L. RNA helicase activity of Semliki Forest virus replicase protein NSP2. FEBS Lett. 1999 Apr 1;448(1):19-22. PMID:10217401
  14. ↑ Vasiljeva L, Merits A, Auvinen P, Kaariainen L. Identification of a novel function of the alphavirus capping apparatus. RNA 5'-triphosphatase activity of Nsp2. J Biol Chem. 2000 Jun 9;275(23):17281-7. PMID:10748213 doi:http://dx.doi.org/10.1074/jbc.M910340199
  15. ↑ Sawicki DL, Perri S, Polo JM, Sawicki SG. Role for nsP2 proteins in the cessation of alphavirus minus-strand synthesis by host cells. J Virol. 2006 Jan;80(1):360-71. PMID:16352561 doi:http://dx.doi.org/10.1128/JVI.80.1.360-371.2006
  16. ↑ Akhrymuk I, Kulemzin SV, Frolova EI. Evasion of the innate immune response: the Old World alphavirus nsP2 protein induces rapid degradation of Rpb1, a catalytic subunit of RNA polymerase II. J Virol. 2012 Jul;86(13):7180-91. doi: 10.1128/JVI.00541-12. Epub 2012 Apr 18. PMID:22514352 doi:http://dx.doi.org/10.1128/JVI.00541-12
  17. ↑ Rikkonen M, Peranen J, Kaariainen L. ATPase and GTPase activities associated with Semliki Forest virus nonstructural protein nsP2. J Virol. 1994 Sep;68(9):5804-10. PMID:8057461
  18. ↑ Ahola T, Kaariainen L. Reaction in alphavirus mRNA capping: formation of a covalent complex of nonstructural protein nsP1 with 7-methyl-GMP. Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):507-11. PMID:7831320
  19. ↑ Ahola T, Laakkonen P, Vihinen H, Kaariainen L. Critical residues of Semliki Forest virus RNA capping enzyme involved in methyltransferase and guanylyltransferase-like activities. J Virol. 1997 Jan;71(1):392-7. PMID:8985362
  20. ↑ Laakkonen P, Auvinen P, Kujala P, Kaariainen L. Alphavirus replicase protein NSP1 induces filopodia and rearrangement of actin filaments. J Virol. 1998 Dec;72(12):10265-9. PMID:9811773
  21. ↑ Gomez de Cedron M, Ehsani N, Mikkola ML, Garcia JA, Kaariainen L. RNA helicase activity of Semliki Forest virus replicase protein NSP2. FEBS Lett. 1999 Apr 1;448(1):19-22. PMID:10217401
  22. ↑ Vasiljeva L, Merits A, Auvinen P, Kaariainen L. Identification of a novel function of the alphavirus capping apparatus. RNA 5'-triphosphatase activity of Nsp2. J Biol Chem. 2000 Jun 9;275(23):17281-7. PMID:10748213 doi:http://dx.doi.org/10.1074/jbc.M910340199
  23. ↑ Sawicki DL, Perri S, Polo JM, Sawicki SG. Role for nsP2 proteins in the cessation of alphavirus minus-strand synthesis by host cells. J Virol. 2006 Jan;80(1):360-71. PMID:16352561 doi:http://dx.doi.org/10.1128/JVI.80.1.360-371.2006
  24. ↑ Akhrymuk I, Kulemzin SV, Frolova EI. Evasion of the innate immune response: the Old World alphavirus nsP2 protein induces rapid degradation of Rpb1, a catalytic subunit of RNA polymerase II. J Virol. 2012 Jul;86(13):7180-91. doi: 10.1128/JVI.00541-12. Epub 2012 Apr 18. PMID:22514352 doi:http://dx.doi.org/10.1128/JVI.00541-12
  25. ↑ Rikkonen M, Peranen J, Kaariainen L. ATPase and GTPase activities associated with Semliki Forest virus nonstructural protein nsP2. J Virol. 1994 Sep;68(9):5804-10. PMID:8057461
  26. ↑ Ahola T, Kaariainen L. Reaction in alphavirus mRNA capping: formation of a covalent complex of nonstructural protein nsP1 with 7-methyl-GMP. Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):507-11. PMID:7831320
  27. ↑ Ahola T, Laakkonen P, Vihinen H, Kaariainen L. Critical residues of Semliki Forest virus RNA capping enzyme involved in methyltransferase and guanylyltransferase-like activities. J Virol. 1997 Jan;71(1):392-7. PMID:8985362
  28. ↑ Laakkonen P, Auvinen P, Kujala P, Kaariainen L. Alphavirus replicase protein NSP1 induces filopodia and rearrangement of actin filaments. J Virol. 1998 Dec;72(12):10265-9. PMID:9811773
  29. ↑ Gomez de Cedron M, Ehsani N, Mikkola ML, Garcia JA, Kaariainen L. RNA helicase activity of Semliki Forest virus replicase protein NSP2. FEBS Lett. 1999 Apr 1;448(1):19-22. PMID:10217401
  30. ↑ Vasiljeva L, Merits A, Auvinen P, Kaariainen L. Identification of a novel function of the alphavirus capping apparatus. RNA 5'-triphosphatase activity of Nsp2. J Biol Chem. 2000 Jun 9;275(23):17281-7. PMID:10748213 doi:http://dx.doi.org/10.1074/jbc.M910340199
  31. ↑ Sawicki DL, Perri S, Polo JM, Sawicki SG. Role for nsP2 proteins in the cessation of alphavirus minus-strand synthesis by host cells. J Virol. 2006 Jan;80(1):360-71. PMID:16352561 doi:http://dx.doi.org/10.1128/JVI.80.1.360-371.2006
  32. ↑ Akhrymuk I, Kulemzin SV, Frolova EI. Evasion of the innate immune response: the Old World alphavirus nsP2 protein induces rapid degradation of Rpb1, a catalytic subunit of RNA polymerase II. J Virol. 2012 Jul;86(13):7180-91. doi: 10.1128/JVI.00541-12. Epub 2012 Apr 18. PMID:22514352 doi:http://dx.doi.org/10.1128/JVI.00541-12
  33. ↑ Rikkonen M, Peranen J, Kaariainen L. ATPase and GTPase activities associated with Semliki Forest virus nonstructural protein nsP2. J Virol. 1994 Sep;68(9):5804-10. PMID:8057461
  34. ↑ Ahola T, Kaariainen L. Reaction in alphavirus mRNA capping: formation of a covalent complex of nonstructural protein nsP1 with 7-methyl-GMP. Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):507-11. PMID:7831320
  35. ↑ Ahola T, Laakkonen P, Vihinen H, Kaariainen L. Critical residues of Semliki Forest virus RNA capping enzyme involved in methyltransferase and guanylyltransferase-like activities. J Virol. 1997 Jan;71(1):392-7. PMID:8985362
  36. ↑ Laakkonen P, Auvinen P, Kujala P, Kaariainen L. Alphavirus replicase protein NSP1 induces filopodia and rearrangement of actin filaments. J Virol. 1998 Dec;72(12):10265-9. PMID:9811773
  37. ↑ Gomez de Cedron M, Ehsani N, Mikkola ML, Garcia JA, Kaariainen L. RNA helicase activity of Semliki Forest virus replicase protein NSP2. FEBS Lett. 1999 Apr 1;448(1):19-22. PMID:10217401
  38. ↑ Vasiljeva L, Merits A, Auvinen P, Kaariainen L. Identification of a novel function of the alphavirus capping apparatus. RNA 5'-triphosphatase activity of Nsp2. J Biol Chem. 2000 Jun 9;275(23):17281-7. PMID:10748213 doi:http://dx.doi.org/10.1074/jbc.M910340199
  39. ↑ Sawicki DL, Perri S, Polo JM, Sawicki SG. Role for nsP2 proteins in the cessation of alphavirus minus-strand synthesis by host cells. J Virol. 2006 Jan;80(1):360-71. PMID:16352561 doi:http://dx.doi.org/10.1128/JVI.80.1.360-371.2006
  40. ↑ Akhrymuk I, Kulemzin SV, Frolova EI. Evasion of the innate immune response: the Old World alphavirus nsP2 protein induces rapid degradation of Rpb1, a catalytic subunit of RNA polymerase II. J Virol. 2012 Jul;86(13):7180-91. doi: 10.1128/JVI.00541-12. Epub 2012 Apr 18. PMID:22514352 doi:http://dx.doi.org/10.1128/JVI.00541-12
  41. ↑ Kristensen O. Crystal structure of the G3BP2 NTF2-like domain in complex with a canonical FGDF motif peptide. Biochem Biophys Res Commun. 2015 Sep 26. pii: S0006-291X(15)30640-9. doi:, 10.1016/j.bbrc.2015.09.123. PMID:26410532 doi:http://dx.doi.org/10.1016/j.bbrc.2015.09.123

5drv, resolution 2.75Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=5drv&oldid=2494559"