7QCX

Two-state liquid NMR Structure of a PDZ2 Domain from hPTP1E, apo form

Summary for 7QCX

• Entry DOI: 10.2210/pdb7qcx/pdb
• NMR Information: BMRB: 34688
• Descriptor: Tyrosine-protein phosphatase non-receptor type 13 (1 entity in total)
• Functional Keywords: protein-protein recognition domain, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 10020.25

Authors

Ashkinadze, D.,Kadavath, H.,Chi, C.,Friedmann, M.,Strotz, D.,Kumari, P.,Minges, M.,Cadalbert, R.,Koenigl, S.,Guentert, P.,Voegeli, B.,Riek, R. (deposition date: 2021-11-25, release date: 2022-09-07, Last modification date: 2024-06-19)

Primary citation

Ashkinadze, D.,Kadavath, H.,Pokharna, A.,Chi, C.N.,Friedmann, M.,Strotz, D.,Kumari, P.,Minges, M.,Cadalbert, R.,Konigl, S.,Guntert, P.,Vogeli, B.,Riek, R.
Atomic resolution protein allostery from the multi-state structure of a PDZ domain.
Nat Commun, 13:6232-6232, 2022

PubMed Abstract: 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.

PubMed: 36266302
DOI: 10.1038/s41467-022-33687-x

Experimental method

SOLUTION NMR