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==Chimeric titin Z1Z2 functionalized with a KLER exogenous peptide from decorin==
<StructureSection load='6sdb' size='340' side='right'caption='[[6sdb]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6sdb]] is a 5 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=6SDB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SDB 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]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <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=6sdb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sdb OCA], [https://pdbe.org/6sdb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6sdb RCSB], [https://www.ebi.ac.uk/pdbsum/6sdb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6sdb ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TITIN_HUMAN TITIN_HUMAN] Defects in TTN are the cause of hereditary myopathy with early respiratory failure (HMERF) [MIM:[https://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:[https://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:[https://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:[https://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:[https://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:[https://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 ==
[https://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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The development of cell culture systems for the naturalistic propagation, self-renewal and differentiation of cells ex vivo is a high goal of molecular engineering. Despite significant success in recent years, the high cost of up-scaling cultures, the need for xeno-free culture conditions, and the degree of mimicry of the natural extracellular matrix attainable in vitro using designer substrates continue to pose obstacles to the translation of cell-based technologies. In this regard, the ZT biopolymer is a protein-based, stable, scalable, and economical cell substrate of high promise. ZT is based on the naturally occurring assembly of two human proteins: titin-Z1Z2 and telethonin. These protein building blocks are robust scaffolds that can be conveniently functionalized with full-length proteins and bioactive peptidic motifs by genetic manipulation, prior to self-assembly. The polymer is, thereby, fully encodable. Functionalized versions of the ZT polymer have been shown to successfully sustain the long-term culturing of human embryonic stem cells (hESCs), human induced pluripotent stem cells (hiPSCs), and murine mesenchymal stromal cells (mMSCs). Pluripotency of hESCs and hiPSCs was retained for the longest period assayed (4 months). Results point to the large potential of the ZT system for the creation of a modular, pluri-functional biomaterial for cell-based applications.

The ZT Biopolymer: A Self-Assembling Protein Scaffold for Stem Cell Applications.,Nesterenko Y, Hill CJ, Fleming JR, Murray P, Mayans O Int J Mol Sci. 2019 Sep 3;20(17). pii: ijms20174299. doi: 10.3390/ijms20174299. PMID:31484291<ref>PMID:31484291</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6sdb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Titin 3D structures|Titin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fleming JR]]
[[Category: Hill C]]
[[Category: Mayans OM]]