2wp3: Difference between revisions

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==Crystal structure of the Titin M10-Obscurin like 1 Ig complex==
The line below this paragraph, containing "STRUCTURE_2wp3", creates the "Structure Box" on the page.
<StructureSection load='2wp3' size='340' side='right'caption='[[2wp3]], [[Resolution|resolution]] 1.48&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[2wp3]] is a 2 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=2WP3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WP3 FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.48&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
{{STRUCTURE_2wp3|  PDB=2wp3  |  SCENE=  }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2wp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wp3 OCA], [https://pdbe.org/2wp3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wp3 RCSB], [https://www.ebi.ac.uk/pdbsum/2wp3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wp3 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/OBSL1_HUMAN OBSL1_HUMAN] Defects in OBSL1 are the cause of 3M syndrome type 2 (3M2) [MIM:[https://omim.org/entry/612921 612921]. An autosomal recessive disorder characterized by severe pre- and postnatal growth retardation, facial dysmorphism, large head circumference, and normal intelligence and endocrine function. Skeletal changes include long slender tubular bones and tall vertebral bodies.<ref>PMID:19481195</ref>
== Function ==
[https://www.uniprot.org/uniprot/OBSL1_HUMAN OBSL1_HUMAN]
== 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/wp/2wp3_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2wp3 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== 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.


===CRYSTAL STRUCTURE OF THE TITIN M10-OBSCURIN LIKE 1 IG COMPLEX===
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<ref>PMID:20133654</ref>


 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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{{ABSTRACT_PUBMED_20133654}}
 
==About this Structure==
[[2wp3]] is a 2 chain structure of [[Titin]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WP3 OCA].


==See Also==
==See Also==
*[[Titin]]
*[[Obscurin|Obscurin]]
 
*[[Titin 3D structures|Titin 3D structures]]
==Reference==
== References ==
<ref group="xtra">PMID:020133654</ref><references group="xtra"/>
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Large Structures]]
[[Category: Fuzukawa, A.]]
[[Category: Fuzukawa A]]
[[Category: Gautel, M.]]
[[Category: Gautel M]]
[[Category: Pernigo, S.]]
[[Category: Pernigo S]]
[[Category: Steiner, R A.]]
[[Category: Steiner RA]]
[[Category: Atp-binding]]
[[Category: Calmodulin-binding]]
[[Category: Cardiomyopathy]]
[[Category: Immunoglobulin domain]]
[[Category: Kelch repeat]]
[[Category: Limb-girdle muscular dystrophy]]
[[Category: Sarcomere]]
[[Category: Serine/threonine-protein kinase]]
[[Category: Transferase-structural protein complex]]

Latest revision as of 11:03, 23 October 2024

Crystal structure of the Titin M10-Obscurin like 1 Ig complexCrystal structure of the Titin M10-Obscurin like 1 Ig complex

Structural highlights

2wp3 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.48Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

OBSL1_HUMAN Defects in OBSL1 are the cause of 3M syndrome type 2 (3M2) [MIM:612921. An autosomal recessive disorder characterized by severe pre- and postnatal growth retardation, facial dysmorphism, large head circumference, and normal intelligence and endocrine function. Skeletal changes include long slender tubular bones and tall vertebral bodies.[1]

Function

OBSL1_HUMAN

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[2]

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

See Also

References

  1. Hanson D, Murray PG, Sud A, Temtamy SA, Aglan M, Superti-Furga A, Holder SE, Urquhart J, Hilton E, Manson FD, Scambler P, Black GC, Clayton PE. The primordial growth disorder 3-M syndrome connects ubiquitination to the cytoskeletal adaptor OBSL1. Am J Hum Genet. 2009 Jun;84(6):801-6. doi: 10.1016/j.ajhg.2009.04.021. Epub 2009 , May 28. PMID:19481195 doi:10.1016/j.ajhg.2009.04.021
  2. 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

2wp3, resolution 1.48Å

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