Layout of titin in the half-sarcomere and atomic structures of titin domains available to date. Shown are two strands of the cardiac N2BA titin isoform. Atomic structures were obtained from the Protein Data Bank; for original references, see the text. X-Ray indicates that the structure was resolved by x-ray crystallography; NMR indicates that the structure was resolved by solution nuclear magnetic resonance spectroscopy. Titin domain nomenclature is according to Ref. 9; note that Ig domain I91 is often called I27 elsewhere in the literature. Z, I, A, and M refer to Z-disk, I-band, A-band, and M-band titin location, respectively. The titin segments are as follows. Ig is the immunoglobulin-like domain region; N2-B is the cardiac-specific region encoded by human titin exon 49; N2-A is the I-band region encoded by human titin exons 102–109; PEVK is the unique sequence (>70% Pro, Glu, Val, and Lys residues); and the FN3-like domain is the fibronectin type 3-like domain.