View source for 3lpw


==Crystal structure of the FnIII-tandem A77-A78 from the A-band of titin==
<StructureSection load='3lpw' size='340' side='right'caption='[[3lpw]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3lpw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The May 2015 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Titin''  by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2015_5 10.2210/rcsb_pdb/mom_2015_5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LPW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LPW 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]] 1.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</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=3lpw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lpw OCA], [https://pdbe.org/3lpw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lpw RCSB], [https://www.ebi.ac.uk/pdbsum/3lpw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lpw 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> 
== 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/lp/3lpw_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3lpw ConSurf].
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== Publication Abstract from PubMed ==
Titin is a large intrasarcomeric protein that, among its many roles in muscle, is thought to modulate the in vivo assembly of the myosin motor filament. This is achieved through the molecular template properties of its A-band region, which is composed of fibronectin type III (FnIII) and immunoglobulin (Ig) domains organized into characteristic 7-domain (D-zone) and 11-domain (C-zone) superrepeats. Currently, there is little knowledge on the structural details of this region of titin. Here we report the conformational characterization of three FnIII tandems, A77-A78, A80-A82, and A84-A86, which are components of the representative fourth C-zone superrepeat. The structure of A77-A78 has been elucidated by X-ray crystallography to 1.65 A resolution, while low-resolution models of A80-A82 and A84-A86 have been calculated using small-angle X-ray scattering. A77-A78 adopts an extended "up-down" domain arrangement, where domains are connected by a hydrophilic three-residue linker sequence. The linker is embedded in a rich network of polar contacts at the domain interface that results in a stiff molecular conformation. The models of A80-A82 and A84-A86, which contain hydrophobic six-residue-long interdomain linkers, equally showed elongated molecular shapes, but with slightly coiled or zigzagged conformations. Small-angle X-ray scattering data further suggested that the long linkers do not result in a noticeable increase in molecular flexibility but lead to semibent domain arrangements. Our findings indicate that the structural characteristics of FnIII tandems from A-band titin contrast markedly with those of poly-Ig tandems from the elastic I-band, which exhibit domain interfaces depleted of interactions and compliant conformations. Furthermore, the analysis of sequence conservation in FnIII domains from A-band titin points to the existence of conformationally defined interfaces at specific superrepeat positions, possibly leading to a periodic and locally ordered architecture supporting the molecular scaffold properties of this region of titin.

The structure of the FnIII Tandem A77-A78 points to a periodically conserved architecture in the myosin-binding region of titin.,Bucher RM, Svergun DI, Muhle-Goll C, Mayans O J Mol Biol. 2010 Sep 3;401(5):843-53. Epub 2010 Jun 11. PMID:20542041<ref>PMID:20542041</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Titin 3D structures|Titin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Titin]]
[[Category: Bucher RM]]
[[Category: Mayans O]]