4lmd

From Proteopedia

(Difference between revisions)

Revision as of 19:20, 5 August 2016

Crystal structure of the JCV large t-antigen origin binding domain

Structural highlights

4lmd is a 2 chain structure with sequence from Human polyomavirus (type jc). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4lif
Gene:	Large T antigen (Human polyomavirus (type JC))
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[LT_POVJC] Isoform large T antigen is a key early protein essential for both driving viral replication and inducing cellular transformation. Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle and by autoregulating the synthesis of viral early mRNA. Displays highly oncogenic activities by corrupting the host cellular checkpoint mechanisms that guard cell division and the transcription, replication, and repair of DNA. Participates in the modulation of cellular gene expression preceeding viral DNA replication. This step involves binding to host key cell cycle regulators retinoblastoma protein RB1/pRb and TP53. Induces the disassembly of host E2F1 transcription factors from RB1, thus promoting transcriptional activation of E2F1-regulated S-phase genes. Inhibits host TP53 binding to DNA, abrogating the ability of TP53 to stimulate gene expression. Plays the role of a TFIID-associated factor (TAF) in transcription initiation for all three RNA polymerases, by stabilizing the TBP-TFIIA complex on promoters. Initiates viral DNA replication and unwinding via interactions with the viral origin of replication. Binds two adjacent sites in the SV40 origin. The replication fork movement is facilitated by Large T antigen helicase activity. Activates the transcription of viral late mRNA, through host TBP and TFIIA stabilization. Interferes with histone deacetylation mediated by HDAC1, leading to activation of transcription (By similarity).

Publication Abstract from PubMed

JC virus is a member of the Polyomavirus family of DNA tumor viruses and the causative agent of progressive multifocal leukoencephalopathy (PML). PML is a disease that occurs primarily in people who are immunocompromised and is usually fatal. As with other Polyomavirus family members, the replication of JC virus (JCV) DNA is dependent upon the virally encoded protein T-antigen. To further our understanding of JCV replication, we have determined the crystal structure of the origin-binding domain (OBD) of JCV T-antigen. This structure provides the first molecular understanding of JCV T-ag replication functions; for example, it suggests how the JCV T-ag OBD site-specifically binds to the major groove of GAGGC sequences in the origin. Furthermore, these studies suggest how the JCV OBDs interact during subsequent oligomerization events. We also report that the OBD contains a novel "pocket"; which sequesters the A1 & B2 loops of neighboring molecules. Mutagenesis of a residue in the pocket associated with the JCV T-ag OBD interfered with viral replication. Finally, we report that relative to the SV40 OBD, the surface of the JCV OBD contains one hemisphere that is highly conserved and one that is highly variable.

Insights into the initiation of JC virus DNA replication derived from the crystal structure of the T-antigen origin binding domain.,Meinke G, Phelan PJ, Kalekar R, Shin J, Archambault J, Bohm A, Bullock PA PLoS Pathog. 2014 Feb 20;10(2):e1003966. doi: 10.1371/journal.ppat.1003966., eCollection 2014 Feb. PMID:24586168^[1]

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

References

↑ Meinke G, Phelan PJ, Kalekar R, Shin J, Archambault J, Bohm A, Bullock PA. Insights into the initiation of JC virus DNA replication derived from the crystal structure of the T-antigen origin binding domain. PLoS Pathog. 2014 Feb 20;10(2):e1003966. doi: 10.1371/journal.ppat.1003966., eCollection 2014 Feb. PMID:24586168 doi:http://dx.doi.org/10.1371/journal.ppat.1003966

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4lmd"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the JCV large t-antigen origin binding domain==
 <StructureSection load='4lmd' size='340' side='right' caption='[[4lmd]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lif|4lif]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Large T antigen ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10632 Human polyomavirus (type JC)])</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=4lmd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lmd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4lmd RCSB], [http://www.ebi.ac.uk/pdbsum/4lmd 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=4lmd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lmd OCA], [http://pdbe.org/4lmd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lmd RCSB], [http://www.ebi.ac.uk/pdbsum/4lmd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lmd ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4lmd" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Large T Antigen|Large T Antigen]]
 == References ==
 <references/>

4lmd

From Proteopedia

Revision as of 19:20, 5 August 2016

Crystal structure of the JCV large t-antigen origin binding domain

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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