6ZBI

Ternary complex of Calmodulin bound to 2 molecules of NHE1

Summary for 6ZBI

• Entry DOI: 10.2210/pdb6zbi/pdb
• NMR Information: BMRB: 34521
• Descriptor: Calmodulin-1, Sodium/hydrogen exchanger 1, CALCIUM ION (3 entities in total)
• Functional Keywords: complex, nhe1, calmodulin, signaling, metal binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 25691.77

Authors

Prestel, A.,Kragelund, B.B.,Pedersen, E.S.,Pedersen, S.F.,Sjoegaard-Frich, L.M. (deposition date: 2020-06-08, release date: 2021-03-17, Last modification date: 2024-05-15)

Primary citation

Sjogaard-Frich, L.M.,Prestel, A.,Pedersen, E.S.,Severin, M.,Kristensen, K.K.,Olsen, J.G.,Kragelund, B.B.,Pedersen, S.F.
Dynamic Na + /H + exchanger 1 (NHE1) - calmodulin complexes of varying stoichiometry and structure regulate Ca 2+ -dependent NHE1 activation.
Elife, 10:-, 2021

PubMed Abstract: Calmodulin (CaM) engages in Ca-dependent interactions with numerous proteins, including a still incompletely understood physical and functional interaction with the human Na/H-exchanger NHE1. Using nuclear magnetic resonance (NMR) spectroscopy, isothermal titration calorimetry, and fibroblasts stably expressing wildtype and mutant NHE1, we discovered multiple accessible states of this functionally important complex existing in different NHE1:CaM stoichiometries and structures. We determined the NMR solution structure of a ternary complex in which CaM links two NHE1 cytosolic tails. , stoichiometries and affinities could be tuned by variations in NHE1:CaM ratio and calcium ([Ca]) and by phosphorylation of S648 in the first CaM-binding α-helix. In cells, Ca-CaM-induced NHE1 activity was reduced by mimicking S648 phosphorylation and by mutation of the first CaM-binding α-helix, whereas it was unaffected by inhibition of Akt, one of several kinases phosphorylating S648. Our results demonstrate a diversity of NHE1:CaM interaction modes and suggest that CaM may contribute to NHE1 dimerization and thereby augment NHE1 regulation. We propose that a similar structural diversity is of relevance to many other CaM complexes.

PubMed: 33655882
DOI: 10.7554/eLife.60889

Experimental method

SOLUTION NMR