2mmh

From Proteopedia

(Difference between revisions)

Revision as of 03:16, 11 September 2015

Unphosphorylated Mengovirus Leader Protein: NMR Studies of the Phosphorylation of the Mengovirus Leader Protein Reveal Stabilization of Intermolecular Domain Interactions

Structural highlights

2mmh is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2m7y, 2mmg, 2mmi, 2mmk, 2mml
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[POLG_ENMGO] Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes (By similarity). Protein VP0: VP0 precursor is a component of immature procapsids (By similarity). Protein 2B: Affects membrane integrity and cause an increase in membrane permeability (By similarity). Protein 2C: Associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity). Protein 3A, via its hydrophobic domain, serves as membrane anchor (By similarity). Protease 3C: cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind cooperatively to the protease (By similarity). RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity). Protein 2A: is involved in host translation shutoff. Nuclear localization is required for this function (By similarity).

Publication Abstract from PubMed

Cardiovirus Leader (L) proteins induce potent antihost inhibition of active cellular nucleocytoplasmic trafficking by triggering aberrant hyperphosphorylation of nuclear pore proteins (Nup). To achieve this, L binds protein RanGTPase (Ran), a key trafficking regulator, and diverts it into tertiary or quaternary complexes with required kinases. The activity of L is regulated by two phosphorylation events not required for Ran binding. Matched NMR studies on the unphosphorylated, singly, and doubly phosphorylated variants of Mengovirus L (LM) show both modifications act together to partially stabilize a short internal alpha-helix comprising LM residues 43-46. This motif implies that ionic and Van der Waals forces contributed by phosphorylation help organize downstream residues 48-67 into a new interface. The full structure of LM as bound to Ran (unlabeled) and Ran (216 aa) as bound by LM (unlabeled) places LM into the BP1 binding site of Ran, wrapped by the conformational flexible COOH tail. The arrangement explains the tight KD for this complex and places the LM zinc finger and phosphorylation interface as surface exposed and available for subsequent reactions. The core structure of Ran, outside the COOH tail, is not altered by LM binding and remains accessible for canonical RanGTP partner interactions. Pull-down assays identify at least one putative Ran:LM partner as an exportin, Crm1, or CAS. A model of Ran:LM:Crm1, based on the new structures suggests LM phosphorylation status may mediate Ran's selection of exportin(s) and cargo(s), perverting these native trafficking elements into the lethal antihost Nup phosphorylation pathways.

Solution structures of Mengovirus Leader protein, its phosphorylated derivatives, and in complex with nuclear transport regulatory protein, RanGTPase.,Bacot-Davis VR, Ciomperlik JJ, Basta HA, Cornilescu CC, Palmenberg AC Proc Natl Acad Sci U S A. 2014 Oct 20. pii: 201411098. PMID:25331866^[1]

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

References

↑ Bacot-Davis VR, Ciomperlik JJ, Basta HA, Cornilescu CC, Palmenberg AC. Solution structures of Mengovirus Leader protein, its phosphorylated derivatives, and in complex with nuclear transport regulatory protein, RanGTPase. Proc Natl Acad Sci U S A. 2014 Oct 20. pii: 201411098. PMID:25331866 doi:http://dx.doi.org/10.1073/pnas.1411098111

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2mmh"

@@ Line 5: / Line 5: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2m7y|2m7y]], [[2mmg|2mmg]], [[2mmi|2mmi]], [[2mmk|2mmk]], [[2mml|2mml]]</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=2mmh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mmh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2mmh RCSB], [http://www.ebi.ac.uk/pdbsum/2mmh PDBsum]</span></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=2mmh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mmh OCA], [http://pdbe.org/2mmh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mmh RCSB], [http://www.ebi.ac.uk/pdbsum/2mmh PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2mmh" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

2mmh

From Proteopedia

Revision as of 03:16, 11 September 2015

Unphosphorylated Mengovirus Leader Protein: NMR Studies of the Phosphorylation of the Mengovirus Leader Protein Reveal Stabilization of Intermolecular Domain Interactions

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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