1wt6

From Proteopedia

(Difference between revisions)

Revision as of 09:04, 21 April 2021

Coiled-Coil domain of DMPK

Structural highlights

1wt6 is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[DMPK_HUMAN] Defects in DMPK are the cause of dystrophia myotonica type 1 (DM1) [MIM:160900]; also known as Steinert disease. A muscular disorder characterized by myotonia, muscle wasting in the distal extremities, cataract, hypogonadism, defective endocrine functions, male baldness and cardiac arrhythmias. Note=The causative mutation is a CTG expansion in the 3'-UTR of the DMPK gene. A length exceeding 50 CTG repeats is pathogenic, while normal individuals have 5 to 37 repeats. Intermediate alleles with 35-49 triplets are not disease-causing but show instability in intergenerational transmissions. Disease severity varies with the number of repeats: mildly affected persons have 50 to 150 repeats, patients with classic DM have 100 to 1,000 repeats, and those with congenital onset can have more than 2,000 repeats.^[1] ^[2] ^[3] ^[4]

Function

[DMPK_HUMAN] Non-receptor serine/threonine protein kinase which is necessary for the maintenance of skeletal muscle structure and function. May play a role in myocyte differentiation and survival by regulating the integrity of the nuclear envelope and the expression of muscle-specific genes. May also phosphorylate PPP1R12A and inhibit the myosin phosphatase activity to regulate myosin phosphorylation. Also critical to the modulation of cardiac contractility and to the maintenance of proper cardiac conduction activity probably through the regulation of cellular calcium homeostasis. Phosphorylates PLN, a regulator of calcium pumps and may regulate sarcoplasmic reticulum calcium uptake in myocytes. May also phosphorylate FXYD1/PLM which is able to induce chloride currents. May also play a role in synaptic plasticity.^[5] ^[6] ^[7] ^[8] ^[9] ^[10]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Self-assembly via coiled-coil domains (CC) is crucial for the regulation of the dystrophia myotonica kinase (DMPK) -related family of kinases. These CC domains are thought to form dimeric arrangements and thus to mediate dimerization in these enzymes. Using size exclusion chromatography combined with multiangle static light scattering, we analyzed the oligomeric state of DMPK as well as that of a truncated variant lacking the CC fraction. Remarkably, both forms were found to assemble into robust dimers. In contrast, the CC domain in isolation yielded trimeric assemblies, indicating that the oligomerization properties of CC domains from this kinase family are more diversified than anticipated. The crystal structure of this CC has been elucidated to 1.6 angstroms resolution and its properties in solution established using sedimentation equilibrium and thermal denaturation. These data show that, contrary to expectations, the self-assembly of DMPK is not dictated by the association properties of its CC domain. Instead, it appears to be driven by sequence segments flanking both N and C termini of the catalytic kinase fraction, as suggested by models of head-to-head dimers based on small angle X-ray scattering data. Our findings support a shared pattern of assembly across DMPK, ROCKs, and MRCK members of this family.

Molecular insights into the self-assembly mechanism of dystrophia myotonica kinase.,Garcia P, Ucurum Z, Bucher R, Svergun DI, Huber T, Lustig A, Konarev PV, Marino M, Mayans O FASEB J. 2006 Jun;20(8):1142-51. PMID:16770013^[11]

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

References

↑ Fu YH, Pizzuti A, Fenwick RG Jr, King J, Rajnarayan S, Dunne PW, Dubel J, Nasser GA, Ashizawa T, de Jong P, et al.. An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science. 1992 Mar 6;255(5049):1256-8. PMID:1546326
↑ Brook JD, McCurrach ME, Harley HG, Buckler AJ, Church D, Aburatani H, Hunter K, Stanton VP, Thirion JP, Hudson T, et al.. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member. Cell. 1992 Feb 21;68(4):799-808. PMID:1310900
↑ Jansen G, Mahadevan M, Amemiya C, Wormskamp N, Segers B, Hendriks W, O'Hoy K, Baird S, Sabourin L, Lennon G, et al.. Characterization of the myotonic dystrophy region predicts multiple protein isoform-encoding mRNAs. Nat Genet. 1992 Jul;1(4):261-6. PMID:1302022 doi:http://dx.doi.org/10.1038/ng0792-261
↑ Musova Z, Mazanec R, Krepelova A, Ehler E, Vales J, Jaklova R, Prochazka T, Koukal P, Marikova T, Kraus J, Havlovicova M, Sedlacek Z. Highly unstable sequence interruptions of the CTG repeat in the myotonic dystrophy gene. Am J Med Genet A. 2009 Jul;149A(7):1365-74. doi: 10.1002/ajmg.a.32987. PMID:19514047 doi:10.1002/ajmg.a.32987
↑ Bush EW, Helmke SM, Birnbaum RA, Perryman MB. Myotonic dystrophy protein kinase domains mediate localization, oligomerization, novel catalytic activity, and autoinhibition. Biochemistry. 2000 Jul 25;39(29):8480-90. PMID:10913253
↑ Mounsey JP, John JE 3rd, Helmke SM, Bush EW, Gilbert J, Roses AD, Perryman MB, Jones LR, Moorman JR. Phospholemman is a substrate for myotonic dystrophy protein kinase. J Biol Chem. 2000 Jul 28;275(30):23362-7. PMID:10811636 doi:10.1074/jbc.M000899200
↑ Muranyi A, Zhang R, Liu F, Hirano K, Ito M, Epstein HF, Hartshorne DJ. Myotonic dystrophy protein kinase phosphorylates the myosin phosphatase targeting subunit and inhibits myosin phosphatase activity. FEBS Lett. 2001 Mar 30;493(2-3):80-4. PMID:11287000
↑ Kaliman P, Catalucci D, Lam JT, Kondo R, Gutierrez JC, Reddy S, Palacin M, Zorzano A, Chien KR, Ruiz-Lozano P. Myotonic dystrophy protein kinase phosphorylates phospholamban and regulates calcium uptake in cardiomyocyte sarcoplasmic reticulum. J Biol Chem. 2005 Mar 4;280(9):8016-21. Epub 2004 Dec 13. PMID:15598648 doi:10.1074/jbc.M412845200
↑ Tan I, Lai J, Yong J, Li SF, Leung T. Chelerythrine perturbs lamellar actomyosin filaments by selective inhibition of myotonic dystrophy kinase-related Cdc42-binding kinase. FEBS Lett. 2011 May 6;585(9):1260-8. doi: 10.1016/j.febslet.2011.03.054. Epub, 2011 Mar 30. PMID:21457715 doi:10.1016/j.febslet.2011.03.054
↑ Harmon EB, Harmon ML, Larsen TD, Yang J, Glasford JW, Perryman MB. Myotonic dystrophy protein kinase is critical for nuclear envelope integrity. J Biol Chem. 2011 Nov 18;286(46):40296-306. doi: 10.1074/jbc.M111.241455. Epub, 2011 Sep 26. PMID:21949239 doi:10.1074/jbc.M111.241455
↑ Garcia P, Ucurum Z, Bucher R, Svergun DI, Huber T, Lustig A, Konarev PV, Marino M, Mayans O. Molecular insights into the self-assembly mechanism of dystrophia myotonica kinase. FASEB J. 2006 Jun;20(8):1142-51. PMID:16770013 doi:20/8/1142

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1wt6"

@@ Line 3: / Line 3: @@
 <StructureSection load='1wt6' size='340' side='right'caption='[[1wt6]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1wt6]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WT6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WT6 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1wt6]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WT6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WT6 FirstGlance]. <br>
-</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=1wt6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wt6 OCA], [http://pdbe.org/1wt6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1wt6 RCSB], [http://www.ebi.ac.uk/pdbsum/1wt6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1wt6 ProSAT]</span></td></tr>
+</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=1wt6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wt6 OCA], [https://pdbe.org/1wt6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wt6 RCSB], [https://www.ebi.ac.uk/pdbsum/1wt6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wt6 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/DMPK_HUMAN DMPK_HUMAN]] Defects in DMPK are the cause of dystrophia myotonica type 1 (DM1) [MIM:[http://omim.org/entry/160900 160900]]; also known as Steinert disease. A muscular disorder characterized by myotonia, muscle wasting in the distal extremities, cataract, hypogonadism, defective endocrine functions, male baldness and cardiac arrhythmias. Note=The causative mutation is a CTG expansion in the 3'-UTR of the DMPK gene. A length exceeding 50 CTG repeats is pathogenic, while normal individuals have 5 to 37 repeats. Intermediate alleles with 35-49 triplets are not disease-causing but show instability in intergenerational transmissions. Disease severity varies with the number of repeats: mildly affected persons have 50 to 150 repeats, patients with classic DM have 100 to 1,000 repeats, and those with congenital onset can have more than 2,000 repeats.<ref>PMID:1546326</ref> <ref>PMID:1310900</ref> <ref>PMID:1302022</ref> <ref>PMID:19514047</ref>
+[[https://www.uniprot.org/uniprot/DMPK_HUMAN DMPK_HUMAN]] Defects in DMPK are the cause of dystrophia myotonica type 1 (DM1) [MIM:[https://omim.org/entry/160900 160900]]; also known as Steinert disease. A muscular disorder characterized by myotonia, muscle wasting in the distal extremities, cataract, hypogonadism, defective endocrine functions, male baldness and cardiac arrhythmias. Note=The causative mutation is a CTG expansion in the 3'-UTR of the DMPK gene. A length exceeding 50 CTG repeats is pathogenic, while normal individuals have 5 to 37 repeats. Intermediate alleles with 35-49 triplets are not disease-causing but show instability in intergenerational transmissions. Disease severity varies with the number of repeats: mildly affected persons have 50 to 150 repeats, patients with classic DM have 100 to 1,000 repeats, and those with congenital onset can have more than 2,000 repeats.<ref>PMID:1546326</ref> <ref>PMID:1310900</ref> <ref>PMID:1302022</ref> <ref>PMID:19514047</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/DMPK_HUMAN DMPK_HUMAN]] Non-receptor serine/threonine protein kinase which is necessary for the maintenance of skeletal muscle structure and function. May play a role in myocyte differentiation and survival by regulating the integrity of the nuclear envelope and the expression of muscle-specific genes. May also phosphorylate PPP1R12A and inhibit the myosin phosphatase activity to regulate myosin phosphorylation. Also critical to the modulation of cardiac contractility and to the maintenance of proper cardiac conduction activity probably through the regulation of cellular calcium homeostasis. Phosphorylates PLN, a regulator of calcium pumps and may regulate sarcoplasmic reticulum calcium uptake in myocytes. May also phosphorylate FXYD1/PLM which is able to induce chloride currents. May also play a role in synaptic plasticity.<ref>PMID:10913253</ref> <ref>PMID:10811636</ref> <ref>PMID:11287000</ref> <ref>PMID:15598648</ref> <ref>PMID:21457715</ref> <ref>PMID:21949239</ref>
+[[https://www.uniprot.org/uniprot/DMPK_HUMAN DMPK_HUMAN]] Non-receptor serine/threonine protein kinase which is necessary for the maintenance of skeletal muscle structure and function. May play a role in myocyte differentiation and survival by regulating the integrity of the nuclear envelope and the expression of muscle-specific genes. May also phosphorylate PPP1R12A and inhibit the myosin phosphatase activity to regulate myosin phosphorylation. Also critical to the modulation of cardiac contractility and to the maintenance of proper cardiac conduction activity probably through the regulation of cellular calcium homeostasis. Phosphorylates PLN, a regulator of calcium pumps and may regulate sarcoplasmic reticulum calcium uptake in myocytes. May also phosphorylate FXYD1/PLM which is able to induce chloride currents. May also play a role in synaptic plasticity.<ref>PMID:10913253</ref> <ref>PMID:10811636</ref> <ref>PMID:11287000</ref> <ref>PMID:15598648</ref> <ref>PMID:21457715</ref> <ref>PMID:21949239</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

1wt6

From Proteopedia

Revision as of 09:04, 21 April 2021

Coiled-Coil domain of DMPK

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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