Abstract
An intrinsically disordered protein (IDP) lacks a stable three-dimensional structure, while it folds into a specific structure when it binds to a target molecule. In some IDP-target complexes, not all target binding surfaces are exposed on the outside, and intermediate states are observed in their binding processes. We consider that stepwise target recognition via intermediate states is a characteristic of IDP binding to targets with "hidden" binding sites. To investigate IDP binding to hidden target binding sites, we constructed an IDP lattice model based on the HP model. In our model, the IDP is modeled as a chain and the target is modeled as a highly coarse-grained object. We introduced motion and internal interactions to the target to hide its binding sites. In the case of unhidden binding sites, a two-state transition between the free states and a bound state is observed, and we consider that this represents coupled folding and binding. Introducing hidden binding sites, we found an intermediate bound state in which the IDP forms various structures to temporarily stabilize the complex. The intermediate state provides a scaffold for the IDP to access the hidden binding site. We call this process multiform binding. We conclude that structural flexibility of IDPs enables them to access hidden binding sites and this is a functional advantage of IDPs.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.