View source for 7ksp


==Crystal structure of hSAMD9_DBD with DNA==
<StructureSection load='7ksp' size='340' side='right'caption='[[7ksp]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ksp]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=7KSP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KSP 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]] 2.8&#8491;</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=7ksp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ksp OCA], [https://pdbe.org/7ksp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ksp RCSB], [https://www.ebi.ac.uk/pdbsum/7ksp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ksp ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SAMD9_HUMAN SAMD9_HUMAN] MIRAGE syndrome;Familial normophosphatemic tumoral calcinosis. The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry. Germline mutations in SAMD9 with a suppressive effect on the cell cycle are associated with somatic loss of the chromosome 7 harboring the mutant allele. This results in the deletion of several genes and predisposes to the development of myelodysplastic syndrome and acute myelogenous leukemia.<ref>PMID:30046003</ref> 
== Function ==
[https://www.uniprot.org/uniprot/SAMD9_HUMAN SAMD9_HUMAN] Double-stranded nucleic acid binding that acts as a an antiviral factor by playing an essential role in the formation of cytoplasmic antiviral granules (PubMed:25428864, PubMed:28157624). May play a role in the inflammatory response to tissue injury and the control of extra-osseous calcification, acting as a downstream target of TNF-alpha signaling. Involved in the regulation of EGR1, in coordination with RGL2. May be involved in endosome fusion.<ref>PMID:16960814</ref> <ref>PMID:18094730</ref> <ref>PMID:21160498</ref> <ref>PMID:24029230</ref> <ref>PMID:25428864</ref> <ref>PMID:28157624</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
SAMD9 and SAMD9L (SAMD9/9L) are antiviral factors and tumor suppressors, playing a critical role in innate immune defense against poxviruses and the development of myeloid tumors. SAMD9/9L mutations with a gain-of-function (GoF) in inhibiting cell growth cause multisystem developmental disorders including many pediatric myelodysplastic syndromes. Predicted to be multidomain proteins with an architecture like that of the NOD-like receptors, SAMD9/9L molecular functions and domain structures are largely unknown. Here, we identified a SAMD9/9L effector domain that functions by binding to double-stranded nucleic acids (dsNA) and determined the crystal structure of the domain in complex with DNA. Aided with precise mutations that differentially perturb dsNA binding, we demonstrated that the antiviral and antiproliferative functions of the wild-type and GoF SAMD9/9L variants rely on dsNA binding by the effector domain. Furthermore, we showed that GoF variants inhibit global protein synthesis, reduce translation elongation, and induce proteotoxic stress response, which all require dsNA binding by the effector domain. The identification of the structure and function of a SAMD9/9L effector domain provides a therapeutic target for SAMD9/9L-associated human diseases.

Structure and function of an effector domain in antiviral factors and tumor suppressors SAMD9 and SAMD9L.,Peng S, Meng X, Zhang F, Pathak PK, Chaturvedi J, Coronado J, Morales M, Mao Y, Qian SB, Deng J, Xiang Y Proc Natl Acad Sci U S A. 2022 Jan 25;119(4):e2116550119. doi: , 10.1073/pnas.2116550119. PMID:35046037<ref>PMID:35046037</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ksp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Deng J]]
[[Category: Pathak P]]
[[Category: Peng S]]
[[Category: Xiang Y]]