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| | <StructureSection load='2wwm' size='340' side='right'caption='[[2wwm]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='2wwm' size='340' side='right'caption='[[2wwm]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2wwm]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WWM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2WWM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2wwm]] is a 4 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=2WWM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WWM FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</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'>[https://proteopedia.org/fgij/fg.htm?mol=2wwm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wwm OCA], [https://pdbe.org/2wwm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wwm RCSB], [https://www.ebi.ac.uk/pdbsum/2wwm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wwm ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/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> | | </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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| | *[[Obscurin|Obscurin]] | | *[[Obscurin|Obscurin]] |
| - | *[[Titin|Titin]] | + | *[[Titin 3D structures|Titin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Non-specific serine/threonine protein kinase]]
| + | [[Category: Fukuzawa A]] |
| - | [[Category: Fukuzawa, A]] | + | [[Category: Gautel M]] |
| - | [[Category: Gautel, M]] | + | [[Category: Pernigo S]] |
| - | [[Category: Pernigo, S]] | + | [[Category: Steiner RA]] |
| - | [[Category: Steiner, R A]] | + | |
| - | [[Category: Calmodulin-binding]]
| + | |
| - | [[Category: Cardiomyopathy]]
| + | |
| - | [[Category: Immunoglobulin domain]]
| + | |
| - | [[Category: Limb-girdle muscular dystrophy]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Sarcomere]]
| + | |
| - | [[Category: Serine/threonine-protein kinase]]
| + | |
| - | [[Category: Tpr repeat]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transferase-structural protein complex]]
| + | |
| Structural highlights
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
- ↑ 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
- ↑ 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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