Troponin structure and function: a view of recent progress

Figures

• 

  Fig. 1. Model of the muscle thin filament based on the coordinates published by Pirani et al. (2006) showing the likely arrangement of actin (white), tropomyosin (red) and troponin (TnC pink, TnI magenta, TnT yellow), based on electron microscopy and X-ray diffraction. The barbed end (Z- band end) of the actin filament is on the left of the figure. (Color figure online)

• 

  Fig. 2. Front and back view of the 46 kDa core domain of human cardiac Troponin in the Ca2+-activated form. TnC is depicted in blue, TnT in green and TnI in red. PDB accession code 1J1D (Takeda et al. 2003). (Color figure online)

• 

  Fig. 3. The three most populated structures of human cardiac troponin determined by molecular dynamics simulations overlaid over the Takeda et al. structure of hcTn (pale structure) TnC is depicted in blue, TnT in green and TnI in red (Zamora 2019). (Color figure online)

• 

  Fig. 4. The cTnC molecule with its nine helices highlighted. Subunits cTnI and cTnT are transparent for clarity. The troponin structure is the original Takeda structure with the disordered segments of TnI and TnT modelled (Zamora et al. 2016)

• 

  Fig. 5. Sequence and secondary structure of cTnC N-terminal domain. Numbering is for human cardiac troponin C (P63316)

• 

  Fig. 6. Ca2+ dependent changes in the structure of the N-terminal lobe of skeletal troponin C. These images are from the X-ray structure of whole skeletal muscle troponin (1ytz and 1yv0) (Vinogradova et al. 2005) with TnI and TnT edited out for clarity. Thin blue lines are putative hydrogen bonds. Thin red lines are the residues of the hydrophobic patch. a Ribbon diagram of (left) the Ca2+-saturated sTnC and (right) Ca2+-free TnC, viewed from above the short beta sheet formed by amino acids just preceding helices B and D. This structure is disrupted, the two EF hands (AB and CD) move away from each other and the angle between helix A and B changes from 135° to 81° in the absence of Ca2+. b Hydrophobicity surface rendering of sTnC, viewed from the underneath. Maximum hydrophobicity is brown and minimum is blue. In the Ca2+ bound state an extensive hydrophobic surface is presented to the TnI switch peptide (see Fig. 8) (left) that is closed off in the absence of Ca2+ (right). (Color figure online)

• 

  Fig. 7. The cTnI molecule with its relevant structural regions highlighted. Subunits cTnC and cTnT are transparent for clarity. The switch peptide corresponds to Helix H3. Residues 172 to 210 of cTnI are not present in this structure (Zamora et al. 2016)

• 

  Fig. 8. The binding of the skeletal muscle TnI switch peptide, helix3 (green), to the hydrophobic patch of skTnC- Ca2+ (red). The switch peptide is an amphipathic helix with hydrophobic residue on the face interacting with TnC (Ala118, Met121, Leu122, Leu125, Leu126). Rendered from Vinogradova’s X-ray structure 1ytz with segments of TnI C-terminal to Helix 3 and TnT are removed for clarity. (Color figure online)

• 

  Fig. 9. Three models of the structure of the TnI C-terminal domain with the preceding switch peptide docked on TnC Ca2+ (left). Model 1 is (Murakami et al. 2005) (NMR, NOE), model 2 is (Blumenschein et al. 2006) (NMR, CSI) and model 3 is (Takeda et al. 2003). From (Metskas and Rhoades 2015), with permission

• 

  Fig. 10. The cTnT2 domain with its relevant structural regions highlighted. Subunits cTnC and cTnI are transparent for clarity. Residues 1 to 201 of cTnT are not present in this structure

• 

  Fig. 11. Model of troponin T and its interaction with tropomyosin and troponin I. WT average structure (grey) with regions that are structurally sensitive to TNT1 mutations highlighted. The highlighted regions are colored as a function of their subunit: yellow, cTnT; blue, cTnI; and red, cTnC. From (Manning et al. 2012) with permission. (Color figure online)

• 

  Fig. 12. The two most probable conformations of the C-terminus of troponin T determined by molecular dynamics simulations (Zamora et al. 2016). Left is the more common configuration. TnT is in green, magenta bars represent hydrogen bonding between TnT and TnI or TnC. (Color figure online)