%0 Journal Article
%T Atomic resolution protein allostery from the multi-state structure of a PDZ domain.
%A Ashkinadze D
%A Kadavath H
%A Pokharna A
%A Chi CN
%A Friedmann M
%A Strotz D
%A Kumari P
%A Minges M
%A Cadalbert R
%A Königl S
%A Güntert P
%A Vögeli B
%A Riek R
%J Nat Commun
%V 13
%N 1
%D 10 2022 20
%M 36266302
%F 17.694
%R 10.1038/s41467-022-33687-x
%X Recent methodological advances in solution NMR allow the determination of multi-state protein structures and provide insights into structurally and dynamically correlated protein sites at atomic resolution. This is demonstrated in the present work for the well-studied PDZ2 domain of protein human tyrosine phosphatase 1E for which protein allostery had been predicted. Two-state protein structures were calculated for both the free form and in complex with the RA-GEF2 peptide using the exact nuclear Overhauser effect (eNOE) method. In the apo protein, an allosteric conformational selection step comprising almost 60% of the domain was detected with an "open" ligand welcoming state and a "closed" state that obstructs the binding site by changing the distance between the β-sheet 2, α-helix 2, and sidechains of residues Lys38 and Lys72. The observed induced fit-type apo-holo structural rearrangements are in line with the previously published evolution-based analysis covering ~25% of the domain with only a partial overlap with the protein allostery of the open form. These presented structural studies highlight the presence of a dedicated highly optimized and complex dynamic interplay of the PDZ2 domain owed by the structure-dynamics landscape.