4m67

From Proteopedia

(Difference between revisions)

Revision as of 02:40, 25 December 2014

Crystal structure of the human MLKL kinase-like domain

Structural highlights

4m67 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4m66, 4m68, 4m69
Gene:	MLKL (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[MLKL_HUMAN] Required for the execution of programmed necrosis.^[1]

Publication Abstract from PubMed

RIP3 is an essential upstream kinase in necroptosis. The pseudokinase MLKL functions as a substrate of RIP3 to mediate downstream signaling. The molecular mechanism by which RIP3 recognizes and phosphorylates MLKL remains unknown. Here, we report the crystal structures of the mouse RIP3 kinase domain, the MLKL kinase-like domain, and a binary complex between the two. Both RIP3 and MLKL adopt the canonical kinase fold. Free RIP3 exists in an active conformation, whereas MLKL-bound RIP3 is stabilized by AMP-PNP to adopt an inactive conformation. The formation of the RIP3-MLKL complex, involving their respective N- and C-lobes, is accompanied by pronounced conformational changes of the alphaC helix and activation loop in RIP3 and the corresponding structural elements in MLKL. RIP3-mediated MLKL phosphorylation, though important for downstream signaling, is dispensable for stable complex formation between RIP3 and MLKL. Our study serves as a framework for mechanistic understanding of RIP3-mediated necroptotic signaling.

Structural Insights into RIP3-Mediated Necroptotic Signaling.,Xie T, Peng W, Yan C, Wu J, Gong X, Shi Y Cell Rep. 2013 Oct 17;5(1):70-8. doi: 10.1016/j.celrep.2013.08.044. Epub 2013 Oct, 3. PMID:24095729^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wang Z, Jiang H, Chen S, Du F, Wang X. The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell. 2012 Jan 20;148(1-2):228-43. doi: 10.1016/j.cell.2011.11.030. PMID:22265414 doi:http://dx.doi.org/10.1016/j.cell.2011.11.030
↑ Xie T, Peng W, Yan C, Wu J, Gong X, Shi Y. Structural Insights into RIP3-Mediated Necroptotic Signaling. Cell Rep. 2013 Oct 17;5(1):70-8. doi: 10.1016/j.celrep.2013.08.044. Epub 2013 Oct, 3. PMID:24095729 doi:http://dx.doi.org/10.1016/j.celrep.2013.08.044

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4m67"

@@ Line 7: / Line 7: @@
 <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=4m67 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m67 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4m67 RCSB], [http://www.ebi.ac.uk/pdbsum/4m67 PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/MLKL_HUMAN MLKL_HUMAN]] Required for the execution of programmed necrosis.<ref>PMID:22265414</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4m67

From Proteopedia

Revision as of 02:40, 25 December 2014

Crystal structure of the human MLKL kinase-like domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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