View source for 5w0r


==Crystal structure of MBP fused activation-induced cytidine deaminase (AID) in complex with cacodylic acid==
<StructureSection load='5w0r' size='340' side='right'caption='[[5w0r]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5w0r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_O157:H7 Escherichia coli O157:H7] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W0R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W0R 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]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5w0r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w0r OCA], [https://pdbe.org/5w0r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w0r RCSB], [https://www.ebi.ac.uk/pdbsum/5w0r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w0r ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/AICDA_HUMAN AICDA_HUMAN] Hyper-IgM syndrome type 2. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/MALE_ECOLI MALE_ECOLI] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.[https://www.uniprot.org/uniprot/AICDA_HUMAN AICDA_HUMAN] Single-stranded DNA-specific cytidine deaminase. Involved in somatic hypermutation (SHM), gene conversion, and class-switch recombination (CSR) in B-lymphocytes by deaminating C to U during transcription of Ig-variable (V) and Ig-switch (S) region DNA. Required for several crucial steps of B-cell terminal differentiation necessary for efficient antibody responses (PubMed:18722174, PubMed:21385873, PubMed:21518874, PubMed:27716525). May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation (PubMed:21496894).<ref>PMID:18722174</ref> <ref>PMID:21385873</ref> <ref>PMID:21496894</ref> <ref>PMID:21518874</ref> <ref>PMID:27716525</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Activation-induced cytidine deaminase (AID) initiates both class switch recombination (CSR) and somatic hypermutation (SHM) in antibody diversification. Mechanisms of AID targeting and catalysis remain elusive despite its critical immunological roles and off-target effects in tumorigenesis. Here, we produced active human AID and revealed its preferred recognition and deamination of structured substrates. G-quadruplex (G4)-containing substrates mimicking the mammalian immunoglobulin switch regions are particularly good AID substrates in vitro. By solving crystal structures of maltose binding protein (MBP)-fused AID alone and in complex with deoxycytidine monophosphate, we surprisingly identify a bifurcated substrate-binding surface that explains structured substrate recognition by capturing two adjacent single-stranded overhangs simultaneously. Moreover, G4 substrates induce cooperative AID oligomerization. Structure-based mutations that disrupt bifurcated substrate recognition or oligomerization both compromise CSR in splenic B cells. Collectively, our data implicate intrinsic preference of AID for structured substrates and uncover the importance of G4 recognition and oligomerization of AID in CSR.

AID Recognizes Structured DNA for Class Switch Recombination.,Qiao Q, Wang L, Meng FL, Hwang JK, Alt FW, Wu H Mol Cell. 2017 Aug 3;67(3):361-373.e4. doi: 10.1016/j.molcel.2017.06.034. Epub, 2017 Jul 27. PMID:28757211<ref>PMID:28757211</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5w0r" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli O157:H7]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Qiao Q]]
[[Category: Wang L]]
[[Category: Wu H]]