The Intrinsic Dynamics of Tandem Repeat Proteins
Proteins possess unique conformational dynamics known as intrinsic dynamics, spanning various frequencies and sizes. Low-frequency motions, termed global, often underlie their biological function. The structure has evolved to facilitate these functional motions.
This evolution-driven stabilization is evident in molecular machines and tandem repeat (TR) proteins, which act as scaffolds for chaperones, nuclear transport proteins, phosphatases, and transcription regulators. This webserver offers an overview of TR protein dynamics, illustrating their predisposition for structural transitions from unbound to bound conformers. These transitions are facilitated by a few global modes of motion, known as soft modes, which require relatively low energy. ANM (Anisotropic Network Model1) global modes define conformational paths related to functional transitions.
We use different modules of ProDy2,3 to characterize the TR protein's global modes through ANM normal mode analysis and compare them with experimentally observed structural changes. This research builds upon a pilot investigation 4 examining the cooperative mechanics of the PR65 (HEAT repeat) scaffold's role in the allosteric regulation of the phosphatase PP2A. In this webserver we focus on five groups of proteins that benefit from such mechanical aptitude of TR proteins: chaperones, nuclear transport proteins, phosphatases, transcription Regulators, and HUWE1.
References
1Doruker P, Atilgan AR, Bahar I. Dynamics of proteins predicted by molecular dynamics simulations and analytical approaches: Application to a-amylase inhibitor Proteins 2000 40:512-524.
2Zhang S, Krieger JM, Zhang Y, Kaya C, Kaynak B, Mikulska-Ruminska K, Doruker P, Li H, Bahar I ProDy 2.0: Increased scale and scope after 10 years of protein dynamics modelling with Python 2021 Bioinformatics, btab187.
3Bakan A, Meireles LM, Bahar I ProDy: Protein Dynamics Inferred from Theory and Experiments 2011 Bioinformatics 27(11):1575-1577
4Kaynak BT, Dahmani ZL, Doruker P, Banerjee A, Yang SH, Gordon R, Itzhaki LS, Bahar I (2023) Cooperative mechanics of PR65 scaffold underlies the allosteric regulation of the phosphatase PP2A Structure 31, 607-618.
