Journal article
The NMDA Receptor NR1 C1 Region Bound to Calmodulin: Structural Insights into Functional Differences between Homologous Domains
Structure (London), Vol.15(12), pp.1603-1617
2007
DOI: 10.1016/j.str.2007.10.012
PMCID: PMC2246159
PMID: 18073110
Abstract
Calmodulin (CaM) regulates tetrameric N-methyl-D-aspartate receptors (NMDARs) by binding tightly to the C0 and C1 regions of its NR1 subunit. A crystal structure (
2HQW; 1.96 Å) of calcium-saturated CaM bound to NR1C1 (peptide spanning 875–898) showed that NR1 S890, whose phosphorylation regulates membrane localization, was solvent protected, whereas the endoplasmic reticulum retention motif was solvent exposed. NR1 F880 filled the CaM C-domain pocket, whereas T886 was closest to the N-domain pocket. This 1–7 pattern was most similar to that in the CaM-MARCKS complex. Comparison of CaM-ligand wrap-around conformations identified a core tetrad of CaM C-domain residues (FLMM
C) that contacted all ligands consistently. An identical tetrad of N-domain residues (FLMM
N) made variable sets of contacts with ligands. This CaM-NR1C1 structure provides a foundation for designing mutants to test the role of CaM in NR1 trafficking as well as insights into how the homologous CaM domains have different roles in molecular recognition.
Details
- Title: Subtitle
- The NMDA Receptor NR1 C1 Region Bound to Calmodulin: Structural Insights into Functional Differences between Homologous Domains
- Creators
- Zeynep Akyol Ataman - Department of Biochemistry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109, USALokesh Gakhar - Department of Biochemistry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109, USABrenda R Sorensen - Department of Biochemistry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109, USAJohannes W Hell - Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109, USAMadeline A Shea - Department of Biochemistry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109, USA
- Resource Type
- Journal article
- Publication Details
- Structure (London), Vol.15(12), pp.1603-1617
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.str.2007.10.012
- PMID
- 18073110
- PMCID
- PMC2246159
- ISSN
- 0969-2126
- eISSN
- 1878-4186
- Language
- English
- Date published
- 2007
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Biochemistry and Molecular Biology; Medicine Administration
- Record Identifier
- 9984025261502771
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