6NUU

Structure of Calcineurin mutant in complex with NHE1 peptide

Summary for 6NUU

• Entry DOI: 10.2210/pdb6nuu/pdb
• Descriptor: Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform, Calcineurin subunit B type 1, Sodium/hydrogen exchanger 1, ... (9 entities in total)
• Functional Keywords: ser/thr phosphatase, complex, hydrolase, hydrolase-calcium binding protein complex, hydrolase/calcium binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 66201.72

Authors

Wang, X.,Page, R.,Peti, W. (deposition date: 2019-02-02, release date: 2019-07-03, Last modification date: 2023-10-11)

Primary citation

Hendus-Altenburger, R.,Wang, X.,Sjogaard-Frich, L.M.,Pedraz-Cuesta, E.,Sheftic, S.R.,Bendsoe, A.H.,Page, R.,Kragelund, B.B.,Pedersen, S.F.,Peti, W.
Molecular basis for the binding and selective dephosphorylation of Na+/H+exchanger 1 by calcineurin.
Nat Commun, 10:3489-3489, 2019

PubMed Abstract: Very little is known about how Ser/Thr protein phosphatases specifically recruit and dephosphorylate substrates. Here, we identify how the Na/H-exchanger 1 (NHE1), a key regulator of cellular pH homeostasis, is regulated by the Ser/Thr phosphatase calcineurin (CN). NHE1 activity is increased by phosphorylation of NHE1 residue T779, which is specifically dephosphorylated by CN. While it is known that Ser/Thr protein phosphatases prefer pThr over pSer, we show that this preference is not key to this exquisite CN selectivity. Rather a combination of molecular mechanisms, including recognition motifs, dynamic charge-charge interactions and a substrate interaction pocket lead to selective dephosphorylation of pT779. Our data identify T779 as a site regulating NHE1-mediated cellular acid extrusion and provides a molecular understanding of NHE1 substrate selection by CN, specifically, and how phosphatases recruit specific substrates, generally.

PubMed: 31375679
DOI: 10.1038/s41467-019-11391-7

Experimental method

X-RAY DIFFRACTION (2.3 Å)