View source for 6kbd


==fused To-MtbCsm1 with 2dATP==
<StructureSection load='6kbd' size='340' side='right'caption='[[6kbd]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6kbd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv] and [https://en.wikipedia.org/wiki/Thermococcus_onnurineus_NA1 Thermococcus onnurineus NA1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KBD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KBD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DTP:2-DEOXYADENOSINE+5-TRIPHOSPHATE'>DTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=6kbd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kbd OCA], [https://pdbe.org/6kbd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kbd RCSB], [https://www.ebi.ac.uk/pdbsum/6kbd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kbd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CAS10_MYCTU CAS10_MYCTU] CRISPR (clustered regularly interspaced short palindromic repeat) is an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain spacers, sequences complementary to antecedent mobile elements, and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA). The type III-A Csm effector complex binds crRNA and acts as a crRNA-guided RNase, DNase and cyclic oligoadenylate synthase; binding of target RNA cognate to the crRNA is required for all activities (Probable). This CRISPR-Cas system protects bacteria against transformation with plasmids containing DNA homologous to its spacer regions (PubMed:29979631).<ref>PMID:29979631</ref> <ref>PMID:29979631</ref>   This subunit is a single-strand-specific deoxyribonuclease (ssDNase) which digests both linear and circular ssDNA; it has both exo- and endonuclease activity.[UniProtKB:B6YWB8]  ssDNase activity is stimulated in the ternary Csm effector complex; binding of cognate target RNA activates the ssDNase, as the target RNA is degraded ssDNA activity decreases.[UniProtKB:A0A0A7HFE1]  When associated with the ternary Csm effector complex (the crRNA, Cas proteins and a cognate target ssRNA) synthesizes cyclic oligoadenylates (cOA) from ATP. cOAs are second messengers that stimulate the ssRNase activity of Csm6, inducing an antiviral state important for defense against invading nucleic acids.[UniProtKB:A0A0A7HFE1][https://www.uniprot.org/uniprot/CAS10_THEON CAS10_THEON] CRISPR (clustered regularly interspaced short palindromic repeat) is an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain spacers, sequences complementary to antecedent mobile elements, and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA). The type III-A Csm effector complex binds crRNA and acts as a crRNA-guided RNase, DNase and cyclic oligoadenylate synthase; binding of target RNA cognate to the crRNA is required for all activities.[UniProtKB:A0A0A7HFE1]  A single-strand deoxyribonuclease (ssDNase) which digests linear and circular ssDNA; has 5'-3' and 3'-5' exonuclease activity as well as a less efficient endonuclease activity. Has a minimal size requirement; 100 nucleotide ssDNA (nt) is more efficiently digested than 50 or 25 nt ssDNA, while 14 nt ssDNA is not cleaved at all. It has no activity on dsDNA or ssRNA.<ref>PMID:25773141</ref>   ssDNase activity is stimulated in the ternary Csm effector complex; binding of cognate target RNA activates the ssDNase, as the target RNA is degraded ssDNA activity decreases.[UniProtKB:A0A0A7HFE1]  When associated with the ternary Csm effector complex (the crRNA, Cas proteins and a cognate target ssRNA) synthesizes cyclic oligoadenylates (cOA) from ATP. cOAs are second messengers that stimulate the ssRNase activity of Csm6, inducing an antiviral state important for defense against invading nucleic acids.[UniProtKB:A0A0A7HFE1]
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== Publication Abstract from PubMed ==
Prokaryotic CRISPR/Cas systems confer immunity against invading nucleic acids through effector complexes. Csm1, the signature protein of Type III effector complexes, catalyses cyclic oligoadenylate synthesis when in the effector complex, but not when alone, activating the Csm6 nuclease and switching on the antiviral response. Here, we provide biochemical evidence that M. tuberculosis Csm1 (MtbCsm1) has ion-dependent polymerase activity when independent of the effector complex. Structural studies provide supporting evidence that the catalytic core of the MtbCsm1 palm2 domain is almost identical to that of classical DNA polymerase Pol IV, and that the palm1 and B domains function as the other structural elements required (thumb and fingers) for DNA polymerase activity. MtbCsm1 polymerase activity is relatively weak in vitro and its functional relevance in vivo is unknown. Our structural and mutagenesis data suggest that residue K692 in the palm2 domain has been significant in the evolution of Csm1 from a polymerase to a cyclase, and support the notion that the cyclase activity of Csm1 requires the presence of other elements provided by the CRISPR/Cas effector complex. This structural rationale for Csm1 polymerase (alone) and cyclase (within the effector complex) activity should benefit future functional investigations and engineering.

Mycobacterium tuberculosis CRISPR/Cas system Csm1 holds clues to the evolutionary relationship between DNA polymerase and cyclase activity.,Zhang S, Li T, Huo Y, Yang J, Fleming J, Shi M, Wang Y, Wei W, Gu S, Bi L, Jiang T, Zhang H Int J Biol Macromol. 2020 Dec 28;170:140-149. doi:, 10.1016/j.ijbiomac.2020.12.014. PMID:33352158<ref>PMID:33352158</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6kbd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Thermococcus onnurineus NA1]]
[[Category: Huo Y]]
[[Category: Jiang T]]
[[Category: Li T]]