Properties of titin immunoglobulin and fibronectin-3 domains.

Immunoglobulin (Ig) and fibronectin-3 (Fn3) domains are common building blocks of many extracellular proteins involved in ligand recognition and cell adhesion. Ig and Fn3 domains are also the main components of a group of intracellular proteins associated with the contractile apparatus of muscles. The largest of the intracellular group is titin ( 3 MDa), which has key roles in the assembly and elasticity of vertebrate striated muscles. The titin molecule spans one-half of the sarcomere, the repeating contractile unit that gives striated muscle its characteristic striped appearance. Titin interacts with a majority of sarcomere proteins and is also likely to bind a variety of cytoplasmic signaling molecules. The Ig and Fn3 domains are important in titin interactions, whereas the levels of interdomain mobility and structural stability relate directly to mechanical functions. Titin and the other muscle Ig/Fn3 proteins are likely to have a common ancestry. It is plausible that the emergence and evolution of the muscle Ig/Fn3 proteins were closely related to the origin and evolution of multicellularity and cell differentiation. This review summarizes current knowledge regarding the properties of the Ig and Fn3 domains of titin. General properties of titins are presented only briefly and are described in detail in recent reviews (1–3).