|
|
| Line 3: |
Line 3: |
| | <SX load='6p7m' size='340' side='right' viewer='molstar' caption='[[6p7m]], [[Resolution|resolution]] 3.00Å' scene=''> | | <SX load='6p7m' size='340' side='right' viewer='molstar' caption='[[6p7m]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6p7m]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_baa-1259 Atcc baa-1259] and [http://en.wikipedia.org/wiki/Lachnospiraceae_bacterium_nd2006 Lachnospiraceae bacterium nd2006]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P7M OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6P7M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6p7m]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Lachnospiraceae_bacterium_ND2006 Lachnospiraceae bacterium ND2006] and [https://en.wikipedia.org/wiki/Moraxella_bovoculi Moraxella bovoculi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P7M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6P7M FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lbcas12a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1410628 Lachnospiraceae bacterium ND2006]), AAX07_09545 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=386891 ATCC BAA-1259])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[http://proteopedia.org/fgij/fg.htm?mol=6p7m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p7m OCA], [http://pdbe.org/6p7m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p7m RCSB], [http://www.ebi.ac.uk/pdbsum/6p7m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p7m ProSAT]</span></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=6p7m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p7m OCA], [https://pdbe.org/6p7m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6p7m RCSB], [https://www.ebi.ac.uk/pdbsum/6p7m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6p7m ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/A0A182DWE3_9FIRM A0A182DWE3_9FIRM] |
| - | CRISPR-Cas systems provide bacteria and archaea with programmable immunity against mobile genetic elements. Evolutionary pressure by CRISPR-Cas has driven bacteriophage to evolve small protein inhibitors, anti-CRISPRs (Acrs), that block Cas enzyme function by wide-ranging mechanisms. We show here that the inhibitor AcrVA4 uses a previously undescribed strategy to recognize the L. bacterium Cas12a (LbCas12a) pre-crRNA processing nuclease, forming a Cas12a dimer, and allosterically inhibiting DNA binding. The A. species Cas12a (AsCas12a) enzyme, widely used for genome editing applications, contains an ancestral helical bundle that blocks AcrVA4 binding and allows it to escape anti-CRISPR recognition. Using biochemical, microbiological, and human cell editing experiments, we show that Cas12a orthologs can be rendered either sensitive or resistant to AcrVA4 through rational structural engineering informed by evolution. Together, these findings explain a new mode of CRISPR-Cas inhibition and illustrate how structural variability in Cas effectors can drive opportunistic co-evolution of inhibitors by bacteriophage.
| + | |
| - | | + | |
| - | Structural basis for AcrVA4 inhibition of specific CRISPR-Cas12a.,Knott GJ, Cress BF, Liu JJ, Thornton BW, Lew RJ, Al-Shayeb B, Rosenberg DJ, Hammel M, Adler BA, Lobba MJ, Xu M, Arkin AP, Fellmann C, Doudna JA Elife. 2019 Aug 9;8. pii: 49110. doi: 10.7554/eLife.49110. PMID:31397669<ref>PMID:31397669</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6p7m" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Atcc baa-1259]]
| + | [[Category: Lachnospiraceae bacterium ND2006]] |
| - | [[Category: Lachnospiraceae bacterium nd2006]] | + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Doudna, J A]] | + | [[Category: Moraxella bovoculi]] |
| - | [[Category: Knott, G J]] | + | [[Category: Doudna JA]] |
| - | [[Category: Liu, J J]] | + | [[Category: Knott GJ]] |
| - | [[Category: Acrva4]] | + | [[Category: Liu JJ]] |
| - | [[Category: Anti-crispr]]
| + | |
| - | [[Category: Cas12a]]
| + | |
| - | [[Category: Cpf1]]
| + | |
| - | [[Category: Crispr-ca]]
| + | |
| - | [[Category: Lbcas12a]]
| + | |
| - | [[Category: Rna binding protein-rna complex]]
| + | |
