DLG2 (2nd dom.)
DLG2 (2nd dom.): Second PDZ domain of the human discs, large homolog 2 protein
PDB Code: 2BYG
DLG2, also known as PSD-93 or Chapsyn-110, is a member of the MAGUK (members of the membrane-associated guanylate kinase family) multi-domain protein family. It contains three disparate domains including a guanylate kinase domain, an SH3 domain and three PDZ domains that are organised as follows:
All three type of domains are known to play important roles in protein-protein interactions pointing to the role that this family of proteins play within the cell. The proteins that DLG2 are known to interact with include: inward rectifying K+ channels ; ionotrophic NMDA receptors; voltage-dependent K+ channel Kv1.4 and the glutamate receptor delta2.
One of the best characterised interactions is with the PDZ domains and their target proteins. The interaction occurs between the C-terminal four amino acids of the target protein and the PDZ domain. Heteromultimerisation of the DLG2 with the related protein PSD-95 results in the formation of a scaffold that brings together the target proteins. This is an important process in the formation clustering of ion channels, transporters and signalling proteins at the postsynaptic sites where DLG2 is located.
The NMDA receptors, which bind to PSD-93, is involved in pain sensation. Activation of the NMDA receptors cause an increase in a cells response to pain. Disruption of the complexes formed by DLG2 significantly reduces induced chronic pain. Thus DLG2 is a potential target for the treatment of persistent pain.
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