5CMB

Mnemiopsis leidyi ML032222a iGluR LBD R703K mutant glycine complex

Summary for 5CMB

• Entry DOI: 10.2210/pdb5cmb/pdb
• Related: 4YKI 5CMC
• Descriptor: ML032222a iGluR, GLYCINE, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: membrane protein, glutamate receptor, ion channel
• Biological source: Mnemiopsis leidyi (sea walnut)
• Total number of polymer chains: 2
• Total formula weight: 58137.60

Authors

Mayer, M.L.,Thomas, A. (deposition date: 2015-07-16, release date: 2016-07-20, Last modification date: 2024-10-30)

Primary citation

Yu, A.,Alberstein, R.,Thomas, A.,Zimmet, A.,Grey, R.,Mayer, M.L.,Lau, A.Y.
Molecular lock regulates binding of glycine to a primitive NMDA receptor.
Proc.Natl.Acad.Sci.USA, 113:E6786-E6795, 2016

PubMed Abstract: The earliest metazoan ancestors of humans include the ctenophore Mnemiopsis leidyi The genome of this comb jelly encodes homologs of vertebrate ionotropic glutamate receptors (iGluRs) that are distantly related to glycine-activated NMDA receptors and that bind glycine with unusually high affinity. Using ligand-binding domain (LBD) mutants for electrophysiological analysis, we demonstrate that perturbing a ctenophore-specific interdomain Arg-Glu salt bridge that is notably absent from vertebrate AMPA, kainate, and NMDA iGluRs greatly increases the rate of recovery from desensitization, while biochemical analysis reveals a large decrease in affinity for glycine. X-ray crystallographic analysis details rearrangements in the binding pocket stemming from the mutations, and molecular dynamics simulations suggest that the interdomain salt bridge acts as a steric barrier regulating ligand binding and that the free energy required to access open conformations in the glycine-bound LBD is largely responsible for differences in ligand affinity among the LBD variants.

PubMed: 27791085
DOI: 10.1073/pnas.1607010113

Experimental method

X-RAY DIFFRACTION (1.34 Å)