View source for 4an8


==Structure of Thermus thermophilus CasA (Cse1)==
<StructureSection load='4an8' size='340' side='right' caption='[[4an8]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4an8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Thet8 Thet8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AN8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AN8 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TTHB188 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=300852 THET8])</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=4an8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4an8 OCA], [http://pdbe.org/4an8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4an8 RCSB], [http://www.ebi.ac.uk/pdbsum/4an8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4an8 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/CSE1_THET8 CSE1_THET8]] 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 sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA) (By similarity).  A component of Cascade, which participates in CRISPR interference, the third stage of CRISPR immunity. Cascade binds both crRNA and in a sequence-specific manner negatively supercoiled dsDNA target. This leads to the formation of an R-loop in which the crRNA binds the target DNA, displacing the noncomplementary strand. Cas3 is recruited to Cascade, probably via interactions with CasA, nicks target DNA and then unwinds and cleaves the target, leading to DNA degradation and invader neutralization. CasA is not required for formation of Cascade, but probably enhances binding to and subsequent recognition of both target dsDNA and ssDNA (By similarity). 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In bacterial and archaeal CRISPR immune pathways, DNA sequences from invading bacteriophage or plasmids are integrated into CRISPR loci within the host genome, conferring immunity against subsequent infections. The ribonucleoprotein complex Cascade utilizes RNAs generated from these loci to target complementary "nonself" DNA sequences for destruction, while avoiding binding to "self" sequences within the CRISPR locus. Here we show that CasA, the largest protein subunit of Cascade, is required for nonself target recognition and binding. Combining a 2.3 A crystal structure of CasA with cryo-EM structures of Cascade, we have identified a loop that is required for viral defense. This loop contacts a conserved three base pair motif that is required for nonself target selection. Our data suggest a model in which the CasA loop scans DNA for this short motif prior to target destabilization and binding, maximizing the efficiency of DNA surveillance by Cascade.

Mechanism of Foreign DNA Selection in a Bacterial Adaptive Immune System.,Sashital DG, Wiedenheft B, Doudna JA Mol Cell. 2012 Apr 17. PMID:22521690<ref>PMID:22521690</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4an8" style="background-color:#fffaf0;"></div>

==See Also==
*[[Endonuclease|Endonuclease]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Thet8]]
[[Category: Doudna, J A]]
[[Category: Sashital, D G]]
[[Category: Wiedenheft, B]]
[[Category: Casa]]
[[Category: Cascade]]
[[Category: Crispr]]
[[Category: Immune system]]