7o24: Difference between revisions
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The | ==Structure of the foamy viral protease-reverse transcriptase in complex with dsDNA.== | ||
<StructureSection load='7o24' size='340' side='right'caption='[[7o24]], [[Resolution|resolution]] 4.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7o24]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/White-tufted-ear_marmoset_simian_foamy_virus White-tufted-ear marmoset simian foamy virus] 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=7O24 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O24 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]] 4.8Å</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=7o24 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o24 OCA], [https://pdbe.org/7o24 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o24 RCSB], [https://www.ebi.ac.uk/pdbsum/7o24 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o24 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/D5JWV1_9RETR D5JWV1_9RETR] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Reverse transcriptases (RTs) use their DNA polymerase and RNase H activities to catalyze the conversion of single-stranded RNA to double-stranded DNA (dsDNA), a crucial process for the replication of retroviruses. Foamy viruses (FVs) possess a unique RT, which is a fusion with the protease (PR) domain. The mechanism of substrate binding by this enzyme has been unknown. Here, we report a crystal structure of monomeric full-length marmoset FV (MFV) PR-RT in complex with an RNA/DNA hybrid substrate. We also describe a structure of MFV PR-RT with an RNase H deletion in complex with a dsDNA substrate in which the enzyme forms an asymmetric homodimer. Cryo-electron microscopy reconstruction of the full-length MFV PR-RT-dsDNA complex confirmed the dimeric architecture. These findings represent the first structural description of nucleic acid binding by a foamy viral RT and demonstrate its ability to change its oligomeric state depending on the type of bound nucleic acid. IMPORTANCE Reverse transcriptases (RTs) are intriguing enzymes converting single-stranded RNA to dsDNA. Their activity is essential for retroviruses, which are divided into two subfamilies differing significantly in their life cycles: Orthoretrovirinae and Spumaretrovirinae. The latter family is much more ancient and comprises five genera. A unique feature of foamy viral RTs is that they contain N-terminal protease (PR) domains, which are not present in orthoretroviral enzymes. So far, no structural information for full-length foamy viral PR-RT interacting with nucleic substrates has been reported. Here, we present crystal and cryo-electron microscopy structures of marmoset foamy virus (MFV) PR-RT. These structures revealed the mode of binding of RNA/DNA and dsDNA substrates. Moreover, unexpectedly, the structures and biochemical data showed that foamy viral PR-RT can adopt both a monomeric configuration, which is observed in our structures in the presence of an RNA/DNA hybrid, and an asymmetric dimer arrangement, which we observed in the presence of dsDNA. | |||
Structures of Substrate Complexes of Foamy Viral Protease-Reverse Transcriptase.,Nowacka M, Nowak E, Czarnocki-Cieciura M, Jackiewicz J, Skowronek K, Szczepanowski RH, Wohrl BM, Nowotny M J Virol. 2021 Aug 25;95(18):e0084821. doi: 10.1128/JVI.00848-21. Epub 2021 Aug , 25. PMID:34232702<ref>PMID:34232702</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7o24" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: White-tufted-ear marmoset simian foamy virus]] | |||
[[Category: Czarnocki-Cieciura M]] | |||
[[Category: Nowotny M]] | |||
