2YGG

Complex of CaMBR and CaM

Summary for 2YGG

• Entry DOI: 10.2210/pdb2ygg/pdb
• Related: 1G4Y 1NIW 1QX5 1QX7 1Y4E 2BEC 3CLN
• Descriptor: SODIUM/HYDROGEN EXCHANGER 1, CALMODULIN, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (7 entities in total)
• Functional Keywords: metal binding protein-transport protein complex, metal binding protein/transport protein
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Membrane; Multi-pass membrane protein: P19634; Cytoplasm, cytoskeleton, spindle: P62161
• Total number of polymer chains: 2
• Total formula weight: 26360.73

Authors

Koester, S.,Yildiz, O. (deposition date: 2011-04-15, release date: 2011-09-28, Last modification date: 2024-05-08)

Primary citation

Koester, S.,Pavkov-Keller, T.,Kuehlbrandt, W.,Yildiz, O.
Structure of Human Na+/H+ Exchanger Nhe1 Regulatory Region in Complex with Cam and Ca2+
J.Biol.Chem., 286:40954-, 2011

PubMed Abstract: The ubiquitous mammalian Na(+)/H(+) exchanger NHE1 has critical functions in regulating intracellular pH, salt concentration, and cellular volume. The regulatory C-terminal domain of NHE1 is linked to the ion-translocating N-terminal membrane domain and acts as a scaffold for signaling complexes. A major interaction partner is calmodulin (CaM), which binds to two neighboring regions of NHE1 in a strongly Ca(2+)-dependent manner. Upon CaM binding, NHE1 is activated by a shift in sensitivity toward alkaline intracellular pH. Here we report the 2.23 Å crystal structure of the NHE1 CaM binding region (NHE1(CaMBR)) in complex with CaM and Ca(2+). The C- and N-lobes of CaM bind the first and second helix of NHE1(CaMBR), respectively. Both the NHE1 helices and the Ca(2+)-bound CaM are elongated, as confirmed by small angle x-ray scattering analysis. Our x-ray structure sheds new light on the molecular mechanisms of the phosphorylation-dependent regulation of NHE1 and enables us to propose a model of how Ca(2+) regulates NHE1 activity.

PubMed: 21931166
DOI: 10.1074/JBC.M111.286906

Experimental method

X-RAY DIFFRACTION (2.227 Å)