6rpr
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6rpr is ON HOLD Authors: Essawy, N., Samson, C. Description: LEM domain of Emerin mutant T43I in complex with BAF dimer and the Igfold of the lamin...) |
|||
| (2 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==LEM domain of Emerin mutant T43I in complex with BAF dimer and the Igfold of the lamin A/C== | |
| + | <StructureSection load='6rpr' size='340' side='right'caption='[[6rpr]], [[Resolution|resolution]] 2.26Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6rpr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RPR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RPR 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]] 2.26Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6rpr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rpr OCA], [https://pdbe.org/6rpr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rpr RCSB], [https://www.ebi.ac.uk/pdbsum/6rpr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rpr ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/EMD_HUMAN EMD_HUMAN] Defects in EMD are the cause of Emery-Dreifuss muscular dystrophy type 1 (EDMD1) [MIM:[https://omim.org/entry/310300 310300]. A degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects.<ref>PMID:15328537</ref> <ref>PMID:15009215</ref> <ref>PMID:10323252</ref> <ref>PMID:11587540</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/EMD_HUMAN EMD_HUMAN] Stabilizes and promotes the formation of a nuclear actin cortical network. Stimulates actin polymerization in vitro by binding and stabilizing the pointed end of growing filaments. Inhibits beta-catenin activity by preventing its accumulation in the nucleus. Acts by influencing the nuclear accumulation of beta-catenin through a CRM1-dependent export pathway. Links centrosomes to the nuclear envelope via a microtubule association. EMD and BAF are cooperative cofactors of HIV-1 infection. Association of EMD with the viral DNA requires the presence of BAF and viral integrase. The association of viral DNA with chromatin requires the presence of BAF and EMD. Required for proper localization of non-farnesylated prelamin-A/C.<ref>PMID:15328537</ref> <ref>PMID:16858403</ref> <ref>PMID:16680152</ref> <ref>PMID:17785515</ref> <ref>PMID:19323649</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Emerin is a nuclear envelope protein that contributes to genome organization and cell mechanics. Through its N-terminal LAP2-emerin-MAN1 (LEM)-domain, emerin interacts with the DNA-binding protein barrier-to-autointegration (BAF). Emerin also binds to members of the linker of the nucleoskeleton and cytoskeleton (LINC) complex. Mutations in the gene encoding emerin are responsible for the majority of cases of X-linked Emery-Dreifuss muscular dystrophy (X-EDMD). Most of these mutations lead to an absence of emerin. A few missense and short deletion mutations in the disordered region of emerin are also associated with X-EDMD. More recently, missense and short deletion mutations P22L, K37 and T43I were discovered in emerin LEM-domain, associated with isolated atrial cardiac defects (ACD). Here we reveal which defects, at both the molecular and cellular levels, are elicited by these LEM-domain mutations. Whereas K37 mutation impaired the correct folding of the LEM-domain, P22L and T43I had no impact on the 3D structure of emerin. Surprisingly, all three mutants bound to BAF, albeit with a weaker affinity in the case of K37. In human myofibroblasts derived from a patient's fibroblasts, emerin K37 was correctly localized at the inner nuclear membrane, but was present at a significantly lower level, indicating that this mutant is abnormally degraded. Moreover, SUN2 was reduced, and these cells were defective in producing actin stress fibers when grown on a stiff substrate and after cyclic stretches. Altogether, our data suggest that the main effect of mutation K37 is to perturb emerin function within the LINC complex in response to mechanical stress. | ||
| - | + | An Emerin LEM-Domain Mutation Impairs Cell Response to Mechanical Stress.,Essawy N, Samson C, Petitalot A, Moog S, Bigot A, Herrada I, Marcelot A, Arteni AA, Coirault C, Zinn-Justin S Cells. 2019 Jun 10;8(6). pii: cells8060570. doi: 10.3390/cells8060570. PMID:31185657<ref>PMID:31185657</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6rpr" style="background-color:#fffaf0;"></div> |
| - | [[Category: Essawy | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Essawy N]] | ||
| + | [[Category: Samson C]] | ||
Current revision
LEM domain of Emerin mutant T43I in complex with BAF dimer and the Igfold of the lamin A/C
| |||||||||||
