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Nebulin

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Title: Nebulin  
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Nebulin

Nebulin
Solution structure of the SH3 domain from human nebulin.[1]
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; NEB177D; NEM2
External IDs GeneCards:
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt n/a
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

Nebulin is an actin-binding protein which is localized to the thin filament of the sarcomeres in skeletal muscle. It is a very large protein (600-900 kDa) and binds as many as 200 actin monomers. Because its length is proportional to thin filament length, it is believed that nebulin acts as a thin filament "ruler" and regulates thin filament length during sarcomere assembly.[2] Other functions of nebulin, such as a role in cell signaling, remain uncertain.

Nebulin has also been shown to regulate actin-myosin interactions by inhibiting ATPase activity in a calcium-calmodulin sensitive manner.[3]

Mutations in nebulin cause some cases of the autosomal recessive disorder nemaline myopathy.[4]

A smaller member of the nebulin protein family termed nebulette, is expressed in cardiac muscle.

Contents

  • Structure 1
  • Knockout phenotype 2
  • References 3
  • Further reading 4
  • External links 5

Structure

The structure of the SH3 domain of nebulin was determined by NMR.[1] The SH3 domain from nebulin is composed of 60 amino acid residues, of which 30 percent is in the beta sheet secondary structure (7 strands; 18 residues).

Knockout phenotype

As of 2007, two myofibrils. Witt and colleagues[6] had similar results in their mice, which also died postnatally with reduced thin filament length and contractile function. These nebulin-knockout mice are being investigated as animal models of nemaline myopathy.

References

  1. ^ a b ​; Politou AS, Millevoi S, Gautel M, Kolmerer B, Pastore A (February 1998). "SH3 in muscles: solution structure of the SH3 domain from nebulin". J. Mol. Biol. 276 (1): 189–202.  
  2. ^ McElhinny AS, Kazmierski ST, Labeit S, Gregorio CC (Jul 2003). "Nebulin: the nebulous, multifunctional giant of striated muscle". Trends in Cardiovascular Medicine 13 (5): 195–201.  
  3. ^ Root DD, Wang K (Oct 1994). "Calmodulin-sensitive interaction of human nebulin fragments with actin and myosin". Biochemistry 33 (42): 12581–91.  
  4. ^ Pelin K, Hilpelä P, Donner K, Sewry C, Akkari PA, Wilton SD, Wattanasirichaigoon D, Bang ML, Centner T, Hanefeld F, Odent S, Fardeau M, Urtizberea JA, Muntoni F, Dubowitz V, Beggs AH, Laing NG, Labeit S, de la Chapelle A, Wallgren-Pettersson C (Mar 1999). "Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy". Proceedings of the National Academy of Sciences of the United States of America 96 (5): 2305–10.  
  5. ^ Bang ML, Li X, Littlefield R, Bremner S, Thor A, Knowlton KU, Lieber RL, Chen J (Jun 2006). "Nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle". The Journal of Cell Biology 173 (6): 905–16.  
  6. ^ Witt CC, Burkart C, Labeit D, McNabb M, Wu Y, Granzier H, Labeit S (Aug 2006). "Nebulin regulates thin filament length, contractility, and Z-disk structure in vivo". The EMBO Journal 25 (16): 3843–55.  

Further reading

  • Björklund AK, Light S, Sagit R, Elofsson A (Sep 2010). "Nebulin: a study of protein repeat evolution". Journal of Molecular Biology 402 (1): 38–51.  

External links

  • nebulin at the US National Library of Medicine Medical Subject Headings (MeSH)
  • GeneReviews/NCBI/NIH/UW entry on Nemaline Myopathy
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