View source for 6dl4


==Human Titin ZIg10==
<StructureSection load='6dl4' size='340' side='right'caption='[[6dl4]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6dl4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DL4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DL4 FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TTN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6dl4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dl4 OCA], [http://pdbe.org/6dl4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dl4 RCSB], [http://www.ebi.ac.uk/pdbsum/6dl4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dl4 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>  
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== Publication Abstract from PubMed ==
INTRODUCTION: The giant muscular proteins titin and obscurin bind to each other at the Zdisk during muscle development. This binding event is mediated through two domains from each protein: ZIg9/10 from titin and Ig58/59 from obscurin. This interaction helps stabilize and organize the sarcomere; ablation of this binding leads to muscular dystrophy. OBJECTIVE: Here we solve the high-resolution solution structure of titin ZIg10 and further delineate which sections of titin bind to obscurin. MATERIALS AND METHODS: Solution NMR, Circular Dichroism, and SEC-MALS were used to biophysically characterize the titin domains involved in this titin-obscurin interaction. RESULTS AND CONCLUSION: We present the high-resolution solution structure of titin ZIg10. Additionally, we show that titin ZIg9 drives the titin-obscurin interaction, while ZIg10 does not actively participate in the titin-obscurin interaction but instead acts to stabilize ZIg9.

Structural Insights on the Obscurin-Binding Domains in Titin.,Letourneau AG, Wright NT Protein Pept Lett. 2018;25(11):973-979. doi: 10.2174/0929866525666181004102031. PMID:30289063<ref>PMID:30289063</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Titin|Titin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Wright, N T]]
[[Category: Cytoskeleton]]
[[Category: Sarcomere]]
[[Category: Structural protein]]
[[Category: Titin]]