Group:MUZIC:FilaminC
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(New page: Crystal structure of Human Filamin C domain 23, 2nqc {{STRUCTURE_2nqc| PDB=2nqc | SIZE=300| SCENE= |right|CAPTION=Human Filamin C domain 23, [[2nq...)
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Revision as of 15:51, 23 June 2011
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| Human Filamin C domain 23, 2nqc | |||||||||
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| Ligands: | , , | ||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Filamin C
In humans, 3 isoforms of Filamins exist that are coded by 3 different genes. While the genes for Filamin A and B are present on the X chromosome and chromosome 3 respectively, and both show a ubiquitous expression in many tissues, gene for Filamin C is located on the Chromosome 7 and the encoded protein is specifically expressed in muscles and has been predicted to have a Z disc targeting motif. [1]
Structure
Filamin C is an actin binding homodimeric protein composed of two 290 kDa subunits. Each subunit is composed of an α actinin like N terminal actin binding domain (ABD) made up of 2 calponin homology tandem repeats followed by a flexible rod region containing 24 Immunoglobulin like domains (Ig- like) of around 96 residues each. The most C terminal domain (Ig 24) is the self association domain required for its dimerization ability. The presence of 2 flexible calpain sensitive hinges, Hinge 1 between domain 15 and 16 divides the subunit into Rod 1 and Rod 2 domains and Hinge 2 between 23 and 24 separates the dimerization domain from the rest of domains. [2] . Each Ig domain is made of 7 β strands arranged antiparallel in group of 4 and 3 sheets forming a β sandwich. As the three Filamin proteins share around 70% homology over the entire sequence with the exception of the hinges (Van der Flier et al, 2001), not many structures of the Filamin C domains exist in the PDB.
Function
Since its discovery in 1975 as one of the most potent crosslinkers of F- actin [3] , major efforts have been focused to elucidate the role of Filamins as scaffolding and signaling molecule in cells.
• Cross links actin filaments to form Orthogonal branched networks • Physically link actin cytoskeleton to the membrane • Rod 2 seems to have many interacting partners • Scaffold & Signalling
PDBs
2nqcCrystal structure of Ig-like domain 23 from human filamin C
2d7q Solution structure of the 23th Filamin domain from human Filamin C
2d7m Solution structure of the 14th Filamin domain from human Filamin C
2d7n Solution structure of the 16th Filamin domain from human Filamin C
2d7o Solution structure of the 17th Filamin domain from human Filamin C
2d7p Solution structure of the 22th Filamin domain from human Filamin C
1v05 DIMERIZATION OF HUMAN FILAMIN C: CRYSTAL STRUCTURE OF THE DOMAIN 24
Literature Cited
- ↑ Van der Ven PF et al (2000) Indications for a novel muscular dystrophy pathway. gamma-filamin, the muscle- specific filamin isoform, interacts with myotilin. J Cell Biol 151:235–248
- ↑ Van der Flier et al (2001) Structural and functional aspects of filamins. Biochim Biophys Acta. 23; 1538(2-3):99-117
- ↑ Hartwig, J. & Stossel, T. (1975) Isolation and properties of actin, myosin, and a new actin-binding protein in rabbit alveolar macrophages. J. Biol. Chem. 250, 5696–5705
Extra Reading
Ithychanda SS, Qin J. (2011) Evidence for multisite ligand binding and stretching of filamin by integrin and migfilin. Biochemistry. 50(20):4229-31
Kuhn, Frey (2006) The sarcomeric Z-disc: a nodal point in signalling and disease. J Mol Med 84: 446–468
Khurana (2006) Aspects of the Cytoskeleton, Advances in Molecular and Cell Biology, Elsevier, San Diego
Luther (2009) The vertebrate muscle Z-disc: sarcomere anchor for structure and signaling. J Muscle Res Cell Motil 30:171–185
Nakamura F, Osborn TM, Hartemink CA, Hartwig JH, Stossel TP. (2007) Structural basis of filamin A functions. J Cell Biol; 179:1011-25
Nakamura F, Stossel TP, Hartwig JH. (2011) The filamins: organizers of cell structure and function. Cell Adh Migr.; 5(2):160-9.
Outi K. Heikkinen, Salla Ruskamo, Peter V. Konarev, Dmitri I. Svergun, Tatu Iivanainen, Sami M. Heikkinen, Perttu Permi, Harri Koskela, Ilkka Kilpeläinen, and Jari Ylänne, (2009) Atomic Structures of Two Novel Immunoglobulin-like Domain Pairs in the Actin Cross-linking Protein Filamin. J BioChem. 11; 284(37):25450-8
Shatunov et al (2009) In-frame deletion in the seventh immunoglobulin-like repeat of filamin C in a family with myofibrillar myopathy. Eur J Hum Genet. 17(5):656-63.
Stossel TP, Condeelis J, Cooley L, Hartwig JH, Noegel A, Schleicher M, et al. (2001) Filamins as integrators of cell mechanics and signalling. Nat Rev Mol Cell Biol; 2:138-45.
Thompson TG, Chan YM, Hack AA, Brosius M, Rajala M, Lidov HG, et al. (2000) Filamin 2 (FLN2): A muscle-specific sarcoglycan interacting protein. J Cell Biol; 148:115-26.
Vorgerd et al (2005) A Mutation in the Dimerization Domain of Filamin C Causes a Novel Type of Autosomal Dominant Myofibrillar Myopathy. Am. J. Hum. Genet. 77:297–304
Young et al (1998) Molecular structure of the sarcomeric Z-disk: two types of titin interactions lead to an asymmetrical sorting of α-actinin. The EMBO Journal Vol.17 No.6 pp.1614–1624
