Group:MUZIC:Myopalladin

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Revision as of 13:09, 13 July 2011

Introduction

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 alpha-Actinin-based framework 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 sequenceLink title.

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]

• Alpha-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 Alpha-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. ↑ ^{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
2. ↑ 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