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Group:MUZIC:Myopalladin
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==Introduction== | ==Introduction== | ||
<StructureSection load='2dm2' size='500' side='right' caption='NMR structure of the domain Ig1 of human Palladin' | <StructureSection load='2dm2' size='500' side='right' caption='NMR structure of the domain Ig1 of human Palladin' | ||
| - | >Myopalladin (UniProt ID: Q86TC9 [http://www.uniprot.org/uniprot/Q86TC9]) is a protein specific of striated muscles that was identified in a yeast two hybrid screen where the SH3 domain of Nebulin (UniProt ID: P20929 [http://www.uniprot.org/uniprot/P20929],[http://www.proteopedia.org/wiki/index.php/User:Marie-Cecile_Pelissier/Workbench/Nebulin]) was used as a bait. <ref name="Bang">PMID 11309420</ref> It belongs to the family of Actin-Associated Scaffolds, which includes Myotilin, Palladin (UniProt ID: Q8WX93 [http://www.uniprot.org/uniprot/Q8WX93]), and Myopalladin, all three being binding partners of | + | >Myopalladin (UniProt ID: Q86TC9 [http://www.uniprot.org/uniprot/Q86TC9]) is a protein specific of striated muscles that was identified in a yeast two hybrid screen where the SH3 domain of Nebulin (UniProt ID: P20929 [http://www.uniprot.org/uniprot/P20929],[http://www.proteopedia.org/wiki/index.php/User:Marie-Cecile_Pelissier/Workbench/Nebulin]) was used as a bait. <ref name="Bang">PMID 11309420</ref> It belongs to the family of Actin-Associated Scaffolds, which includes Myotilin, Palladin (UniProt ID: Q8WX93 [http://www.uniprot.org/uniprot/Q8WX93]), and Myopalladin, all three being binding partners of α-Actinin. |
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==Function and related diseases== | ==Function and related diseases== | ||
Myopalladin is mostly localised at the Z disk and the I band of the sarcomere in both skeletal and cardiac muscle cells, and was also found to be present in the nucleus. | Myopalladin is mostly localised at the Z disk and the I band of the sarcomere in both skeletal and cardiac muscle cells, and was also found to be present in the nucleus. | ||
| - | It is considered to be an important structural member of the Z/I region of the sarcomere. It is involved in the targeting and anchoring of key sarcomeric components (Nebulin and Nebulette) to the Z-disk and takes part to the | + | It is considered to be an important structural member of the Z/I region of the sarcomere. It is involved in the targeting and anchoring of key sarcomeric components (Nebulin and Nebulette) to the Z-disk and takes part to the α-Actinin-based mesh of the Z-disk. |
Myopalladin is also thought to be related to the Z-disk signaling through its interaction with CARP, a negative regulator of muscle growth. | Myopalladin is also thought to be related to the Z-disk signaling through its interaction with CARP, a negative regulator of muscle growth. | ||
Mutations of the Myopalladin encoding gene were described in patients suffering from Dilated Cardiac Myopathies (DCM). <ref>PMID 18006477</ref> These mutations are associated with a major disorganisation of muscle cells structure and sarcomere breakdown, which would be triggered by the mislocalisation of Myopalladin within the muscle cells. | Mutations of the Myopalladin encoding gene were described in patients suffering from Dilated Cardiac Myopathies (DCM). <ref>PMID 18006477</ref> These mutations are associated with a major disorganisation of muscle cells structure and sarcomere breakdown, which would be triggered by the mislocalisation of Myopalladin within the muscle cells. | ||
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*CARP: The N-terminal region of Myopalladin, going from the N-terminus of the protein to its domain Ig2, was shown to interact with the full length CARP. <ref name="Bang" /> | *CARP: The N-terminal region of Myopalladin, going from the N-terminus of the protein to its domain Ig2, was shown to interact with the full length CARP. <ref name="Bang" /> | ||
| - | * | + | *α-Actinin: The C-terminal region of Myopalladin, going from the domain Ig3 to the C-terminus of the protein, was shown to interact with the EF-hand region of α-Actinin. <ref name="Bang" /> |
===Inserted sequences and their binding partners=== | ===Inserted sequences and their binding partners=== | ||
Revision as of 14:44, 13 July 2011
Contents |
Introduction
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Function and related diseases
Myopalladin is mostly localised at the Z disk and the I band of the sarcomere in both skeletal and cardiac muscle cells, and was also found to be present in the nucleus. It is considered to be an important structural member of the Z/I region of the sarcomere. It is involved in the targeting and anchoring of key sarcomeric components (Nebulin and Nebulette) to the Z-disk and takes part to the α-Actinin-based mesh of the Z-disk. Myopalladin is also thought to be related to the Z-disk signaling through its interaction with CARP, a negative regulator of muscle growth. Mutations of the Myopalladin encoding gene were described in patients suffering from Dilated Cardiac Myopathies (DCM). [2] These mutations are associated with a major disorganisation of muscle cells structure and sarcomere breakdown, which would be triggered by the mislocalisation of Myopalladin within the muscle cells.
Domains and Interactions
Myopalladin comprises 5 Ig domains separated by inserted sequences for which no structural domains could be predicted from the sequence.
Ig domains and their binding partners
The only structural data related to Myopalladin are the NMR structures of Ig domain 1 (PDB code 2DM2 [[1]]) and Ig domain 2 (PDB code 2DM3 [[2]]) of Palladin (homologous to Ig domains 3 and 4 of Myopalladin, respectively).
- CARP: The N-terminal region of Myopalladin, going from the N-terminus of the protein to its domain Ig2, was shown to interact with the full length CARP. [1]
- α-Actinin: The C-terminal region of Myopalladin, going from the domain Ig3 to the C-terminus of the protein, was shown to interact with the EF-hand region of α-Actinin. [1]
Inserted sequences and their binding partners
Myopalladin Ig domains are separated by 6 Inserted Sequences (IS).
- Nebulin/Nebulette: The IS3 comprises a Proline-rich region that has been shown to interact with the SH3 domain of Nebulin and Nebulette. [1]
References
- ↑ 1.0 1.1 1.2 1.3 Bang ML, Mudry RE, McElhinny AS, Trombitas K, Geach AJ, Yamasaki R, Sorimachi H, Granzier H, Gregorio CC, Labeit S. Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies. J Cell Biol. 2001 Apr 16;153(2):413-27. PMID:11309420
- ↑ Duboscq-Bidot L, Xu P, Charron P, Neyroud N, Dilanian G, Millaire A, Bors V, Komajda M, Villard E. Mutations in the Z-band protein myopalladin gene and idiopathic dilated cardiomyopathy. Cardiovasc Res. 2008 Jan;77(1):118-25. Epub 2007 Sep 19. PMID:18006477 doi:10.1093/cvr/cvm015
