Figure 3: All-atom MD simulations of the CypA-CA complex in a helical assembly.

(a) A fully saturated CypA-CA tubular complex model with extensive clashes between CypA and CA and between adjacent CypA molecules. CypA is in blue and CA in grey. (b) A density map averaged from ten helically symmetrized MD models of CypA-CA tubes. Colour scheme is the same as that in Fig 2c. The density is contoured at 2σ. The red box encloses the two CA hexamers in complex with CypA that are shown in e. (c,d) Porcupine representation of the most dominant mode from principal component analysis performed on the trajectories of the bridging (c) and non-bridging (d) binding modes of CypA (blue). (e) Result from an all-atom MD simulation of the CypA-CA complex comprising two CA molecules (orange) and one CypA (blue) within a tubular configuration, shown with two CA hexamers (green). The CA molecules making the dimer interface are in red. (f) An enlarged view of the CypA-CA complex from the boxed region in E rotated 90°, illustrating the two CA binding sites on CypA: site 1 is the canonical binding site and site 2 is the non-canonical binding site (see text). Selective residues at the site 2 interface are labelled. (g) Overlay of the MD CypA-CA model with the crystal structure of the CypA-CsA complex (PDB: 2RMA, CypA in purple and CsA in green), illustrating that CypA interacts with a second CsA at site 2.