Hiroshima University, JAPAN
The functionally relevant inter-domain communication between the domains linked by intrinsically disordered region (IDR) was explored by NMR in combination with small angle X-ray scattering (SAXS). Based on the ensemble structure analyses and the numerical simulations to reproduce the chemical shift changes along with the substrate concentration, we have demonstrated how the domains cooperate to enhance the protein function through the substantially dynamic spatial allocation of the domains.
Pin1, a proline cis/trans isomerase, comprises two domains linked by 10-residue IDR; one is the substrate biding domain to recognize pSer/pThr-Pro motif and the other is the enzyme domain that rotates the Pro peptide bond in the motif. The enzyme domain shows very limited affinity to the substrate, but its binding ability was enhanced by two orders of magnitude in the presence of the substrate binding domain linked by IDR; in which the inter-domain ‘fly-casting’ mechanism plays to keep the substrate bound to Pin1 by tossing and receiving the substrate between the domains, once the substrate in bound to either one of the domains. A new functional aspect of IDR will be addressed.