NMDA Subunit Composition

Question 1

What are the families of subunits and who found them?

Answer 1

Glutamate-binding GluN2 and glycine-binding GluN1 and GluN3 (Traynelis et al., 2010)

Question 2

What do NMDA heterotetramers consist of?

Answer 2

Two ubiquitously expressed GluN1 subunits combined with two GluN2 and/or GluN3 subunits, to form either di- or triheterotetrameric ionotropic receptors

Question 3

How many GluN2 subunits are there and what is the importance of this?

Answer 3

Four types of GluN2 subunits exist (A–D), encoded by four separate genes

Important role in receptor kinetics.

Question 4

What 4 things do all subunits contain?

Answer 4

1. A large extracellular N-terminal domain (NTD)
2. An extracellular bi-lobal agonist-binding domain (LBD)
3. A transmembrane region forming the cation channel
4. An intracellular C-terminal domain (CTD)

Question 5

What does the NTD consist of?

Answer 5

Bilobar structure comprised of an upper R1 and lower R2 lobe which are formed from the first approximately 380 amino acids of the protein

Zn2+ binding site in cleft between R1 and R2

Question 6

Who demonstrated NTD features and in what form of the NTD were these features discerned?

Answer 6

Farina et al.,2011 - main structure

Karakas et al.,2009 - Zn2+ binding site

Crystals

Question 7

Examples of allosteric ligands of NMDAR

Answer 7

ifenprodil

Ro25-6981

Question 8

Where do allosteric ligands bind and who demonstrated this?

Answer 8

Dimer interface of GluN1 and GluN2B subunits

Karakas et al.,2011