The NMDA Receptor NR1 C1 Region Bound to Calmodulin: Structural Insights into Functional Differences between Homologous Domains

Zeynep Akyol Ataman, Lokesh Gakhar, Brenda R. Sorensen, Johannes W Hell, Madeline A. Shea

Research output: Contribution to journalArticle

51 Scopus citations

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 (FLMMC) that contacted all ligands consistently. An identical tetrad of N-domain residues (FLMMN) 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.

Original languageEnglish (US)
Pages (from-to)1603-1617
Number of pages15
JournalStructure
Volume15
Issue number12
DOIs
StatePublished - Dec 13 2007
Externally publishedYes

Keywords

  • CELLBIO
  • MOLNEURO
  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

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