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. 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.
The structure of the SH3 domain of nebulin was determined by NMR. 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).
As of 2007, two knockout mouse models for nebulin have been developed to better understand its in vivo function. Bang and colleagues demonstrated that nebulin-knockout mice die postnatally, have reduced thin filament length, and impaired contractile function. Postnatal sarcomere disorganization and degeneration occurred rapidly in these mice, indicating the nebulin is essential for maintaining the structural integrity of myofibrils. Witt and colleagues 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.
^PDB: 1NEB; 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. doi:10.1006/jmbi.1997.1521. PMID9514727.