7SA5

Two-state solution NMR structure of Apo Pin1

Summary for 7SA5

• Entry DOI: 10.2210/pdb7sa5/pdb
• NMR Information: BMRB: 27579
• Descriptor: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (1 entity in total)
• Functional Keywords: prolyl isomerase, ww domain, isomerase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 18271.31

Authors

Born, A.,Vogeli, B. (deposition date: 2021-09-22, release date: 2021-10-20, Last modification date: 2024-05-15)

Primary citation

Born, A.,Soetbeer, J.,Breitgoff, F.,Henen, M.A.,Sgourakis, N.,Polyhach, Y.,Nichols, P.J.,Strotz, D.,Jeschke, G.,Vogeli, B.
Reconstruction of Coupled Intra- and Interdomain Protein Motion from Nuclear and Electron Magnetic Resonance.
J.Am.Chem.Soc., 143:16055-16067, 2021

PubMed Abstract: Proteins composed of multiple domains allow for structural heterogeneity and interdomain dynamics that may be vital for function. Intradomain structures and dynamics can influence interdomain conformations and . However, no established structure determination method is currently available that can probe the coupling of these motions. The protein Pin1 contains separate regulatory and catalytic domains that sample "extended" and "compact" states, and ligand binding changes this equilibrium. Ligand binding and interdomain distance have been shown to impact the activity of Pin1, suggesting interdomain allostery. In order to characterize the conformational equilibrium of Pin1, we describe a novel method to model the coupling between intra- and interdomain dynamics at atomic resolution using multistate ensembles. The method uses time-averaged nuclear magnetic resonance (NMR) restraints and double electron-electron resonance (DEER) data that resolve distance distributions. While the intradomain calculation is primarily driven by exact nuclear Overhauser enhancements (eNOEs), couplings, and residual dipolar couplings (RDCs), the relative domain distribution is driven by paramagnetic relaxation enhancement (PREs), RDCs, interdomain NOEs, and DEER. Our data support a 70:30 population of the compact and extended states in apo Pin1. A multistate ensemble describes these conformations simultaneously, with distinct conformational differences located in the interdomain interface stabilizing the compact or extended states. We also describe correlated conformations between the catalytic site and interdomain interface that may explain allostery driven by interdomain contact.

PubMed: 34579531
DOI: 10.1021/jacs.1c06289

Experimental method

SOLUTION NMR