View source for 7jse


==Adeno-Associated Virus Origin Binding Domain in complex with ssDNA==
<StructureSection load='7jse' size='340' side='right'caption='[[7jse]], [[Resolution|resolution]] 4.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7jse]] is a 24 chain structure with sequence from [https://en.wikipedia.org/wiki/Adeno-associated_virus_2 Adeno-associated virus 2] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JSE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JSE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.6&#8491;</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=7jse FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jse OCA], [https://pdbe.org/7jse PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jse RCSB], [https://www.ebi.ac.uk/pdbsum/7jse PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jse ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/REP68_AAV2S REP68_AAV2S] Plays an essential role in the initiation of viral DNA synthesis. Binds specifically to an inverted terminal repeat element (ITR) on the 3' and 5' ends of the viral DNA, where it cleaves a site specifically to generate a priming site for initiation of the synthesis of a complementary strand. Plays also a role as transcriptional regulator, DNA helicase and as key factor in site-specific integration of the viral genome. Inhibits the host cell cycle G1/S and G2/M transitions. These arrests may provide essential cellular factors for viral DNA replication.<ref>PMID:9882364</ref> 
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== Publication Abstract from PubMed ==
The adeno-associated virus (AAV) non-structural Rep proteins catalyze all the DNA transactions required for virus viability including, DNA replication, transcription regulation, genome packaging, and during the latent phase, site-specific integration. Rep proteins contain two multifunctional domains: an Origin Binding Domain (OBD) and a SF3 helicase domain (HD). Studies have shown that Rep proteins have a dynamic oligomeric behavior where the nature of the DNA substrate molecule modulates its oligomeric state. In the presence of ssDNA, Rep68 forms a large double-octameric ring complex. To understand the mechanisms underlying AAV Rep function, we investigated the cryo-EM and X-ray structures of Rep68-ssDNA complexes. Surprisingly, Rep68 generates hybrid ring structures where the OBD forms octameric rings while the HD forms heptamers. Moreover, the binding to ATPgammaS promotes a large conformational change in the entire AAA+ domain that leads the HD to form both heptamer and hexamers. The HD oligomerization is driven by an interdomain linker region that acts as a latch to 'catch' the neighboring HD subunit and is flexible enough to permit the formation of different stoichiometric ring structures. Overall, our studies show the structural basis of AAV Rep's structural flexibility required to fulfill its multifunctional role during the AAV life cycle.

The Cryo-EM structure of AAV2 Rep68 in complex with ssDNA reveals a malleable AAA+ machine that can switch between oligomeric states.,Santosh V, Musayev FN, Jaiswal R, Zarate-Perez F, Vandewinkel B, Dierckx C, Endicott M, Sharifi K, Dryden K, Henckaerts E, Escalante CR Nucleic Acids Res. 2020 Dec 16;48(22):12983-12999. doi: 10.1093/nar/gkaa1133. PMID:33270897<ref>PMID:33270897</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Adeno-associated virus 2]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Escalante CR]]