2wwm: Difference between revisions

Revision as of 09:40, 3 October 2018

Crystal structure of the Titin M10-Obscurin like 1 Ig complex in space group P1

Structural highlights

2wwm is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1tnn, 1ncu, 2j8o, 1bpv, 2j8h, 2cpc, 2wp3, 1nct, 2wwk, 2bk8, 1tiu, 2f8v, 1tit, 1waa, 2a38, 1tnm, 1g1c, 1tki, 1ya5
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

In the sarcomeric M-band, the giant ruler proteins titin and obscurin, its small homologue obscurin-like-1 (obsl1), and the myosin cross-linking protein myomesin form a ternary complex that is crucial for the function of the M-band as a mechanical link. Mutations in the last titin immunoglobulin (Ig) domain M10, which interacts with the N-terminal Ig-domains of obscurin and obsl1, lead to hereditary muscle diseases. The M10 domain is unusual not only in that it is a frequent target of disease-linked mutations, but also in that it is the only currently known muscle Ig-domain that interacts with two ligands-obscurin and obsl1-in different sarcomeric subregions. Using x-ray crystallography, we show the structural basis for titin M10 interaction with obsl1 in a novel antiparallel Ig-Ig architecture and unravel the molecular basis of titin-M10 linked myopathies. The severity of these pathologies correlates with the disruption of the titin-obsl1/obscurin complex. Conserved signature residues at the interface account for differences in affinity that direct the cellular sorting in cardiomyocytes. By engineering the interface signature residues of obsl1 to obscurin, and vice versa, their affinity for titin can be modulated similar to the native proteins. In single-molecule force-spectroscopy experiments, both complexes yield at forces of around 30 pN, much lower than those observed for the mechanically stable Z-disk complex of titin and telethonin, suggesting why even moderate weakening of the obsl1/obscurin-titin links has severe consequences for normal muscle functions.

Structural insight into M-band assembly and mechanics from the titin-obscurin-like-1 complex.,Pernigo S, Fukuzawa A, Bertz M, Holt M, Rief M, Steiner RA, Gautel M Proc Natl Acad Sci U S A. 2010 Feb 1. PMID:20133654^[1]

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

References

↑ Pernigo S, Fukuzawa A, Bertz M, Holt M, Rief M, Steiner RA, Gautel M. Structural insight into M-band assembly and mechanics from the titin-obscurin-like-1 complex. Proc Natl Acad Sci U S A. 2010 Feb 1. PMID:20133654

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OCA

[1] Pernigo S, Fukuzawa A, Bertz M, Holt M, Rief M, Steiner RA, Gautel M. Structural insight into M-band assembly and mechanics from the titin-obscurin-like-1 complex. Proc Natl Acad Sci U S A. 2010 Feb 1. PMID:20133654

[1]

@@ Line 1: / Line 1: @@
-==CRYSTAL STRUCTURE OF THE TITIN M10-OBSCURIN LIKE 1 IG COMPLEX IN SPACE GROUP P1==
+==Crystal structure of the Titin M10-Obscurin like 1 Ig complex in space group P1==
 <StructureSection load='2wwm' size='340' side='right' caption='[[2wwm]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
@@ Line 5: / Line 6: @@
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1tnn|1tnn]], [[1ncu|1ncu]], [[2j8o|2j8o]], [[1bpv|1bpv]], [[2j8h|2j8h]], [[2cpc|2cpc]], [[2wp3|2wp3]], [[1nct|1nct]], [[2wwk|2wwk]], [[2bk8|2bk8]], [[1tiu|1tiu]], [[2f8v|2f8v]], [[1tit|1tit]], [[1waa|1waa]], [[2a38|2a38]], [[1tnm|1tnm]], [[1g1c|1g1c]], [[1tki|1tki]], [[1ya5|1ya5]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></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=2wwm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wwm OCA], [http://pdbe.org/2wwm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wwm RCSB], [http://www.ebi.ac.uk/pdbsum/2wwm PDBsum]</span></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=2wwm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wwm OCA], [http://pdbe.org/2wwm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wwm RCSB], [http://www.ebi.ac.uk/pdbsum/2wwm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wwm ProSAT]</span></td></tr>
 </table>
-== Disease ==
-[[http://www.uniprot.org/uniprot/TITIN_HUMAN TITIN_HUMAN]] Defects in TTN are the cause of hereditary myopathy with early respiratory failure (HMERF) [MIM:[http://omim.org/entry/603689 603689]]; also known as Edstrom myopathy. HMERF is an autosomal dominant, adult-onset myopathy with early respiratory muscle involvement.<ref>PMID:15802564</ref>   Defects in TTN are the cause of familial hypertrophic cardiomyopathy type 9 (CMH9) [MIM:[http://omim.org/entry/613765 613765]]. Familial hypertrophic cardiomyopathy is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.<ref>PMID:10462489</ref>   Defects in TTN are the cause of cardiomyopathy dilated type 1G (CMD1G) [MIM:[http://omim.org/entry/604145 604145]]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:11846417</ref> <ref>PMID:11788824</ref> <ref>PMID:16465475</ref>   Defects in TTN are the cause of tardive tibial muscular dystrophy (TMD) [MIM:[http://omim.org/entry/600334 600334]]; also known as Udd myopathy. TMD is an autosomal dominant, late-onset distal myopathy. Muscle weakness and atrophy are usually confined to the anterior compartment of the lower leg, in particular the tibialis anterior muscle. Clinical symptoms usually occur at age 35-45 years or much later.<ref>PMID:12145747</ref> <ref>PMID:12891679</ref>   Defects in TTN are the cause of limb-girdle muscular dystrophy type 2J (LGMD2J) [MIM:[http://omim.org/entry/608807 608807]]. LGMD2J is an autosomal recessive degenerative myopathy characterized by progressive weakness of the pelvic and shoulder girdle muscles. Severe disability is observed within 20 years of onset.  Defects in TTN are the cause of early-onset myopathy with fatal cardiomyopathy (EOMFC) [MIM:[http://omim.org/entry/611705 611705]]. Early-onset myopathies are inherited muscle disorders that manifest typically from birth or infancy with hypotonia, muscle weakness, and delayed motor development. EOMFC is a titinopathy that, in contrast with the previously described examples, involves both heart and skeletal muscle, has a congenital onset, and is purely recessive. This phenotype is due to homozygous out-of-frame TTN deletions, which lead to a total absence of titin's C-terminal end from striated muscles and to secondary CAPN3 depletion.<ref>PMID:17444505</ref>
-== Function ==
-[[http://www.uniprot.org/uniprot/TITIN_HUMAN TITIN_HUMAN]] Key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The size and extensibility of the cross-links are the main determinants of sarcomere extensibility properties of muscle. In non-muscle cells, seems to play a role in chromosome condensation and chromosome segregation during mitosis. Might link the lamina network to chromatin or nuclear actin, or both during interphase.<ref>PMID:9804419</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
    <jmolCheckbox>
-     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ww/2wwm_consurf.spt"</scriptWhenChecked>
+     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ww/2wwm_consurf.spt"</scriptWhenChecked>
      <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
      <text>to colour the structure by Evolutionary Conservation</text>

2wwm: Difference between revisions

Revision as of 09:40, 3 October 2018

Crystal structure of the Titin M10-Obscurin like 1 Ig complex in space group P1

Structural highlights

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

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