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Publication Abstract from PubMed

Scaffold proteins play crucial roles in orchestrating synaptic signaling and plasticity in the excitatory synapses by providing a structural link between glutamatergic receptors, signaling molecules, and neuronal cytoskeletons. FRMPD4 is a neural scaffold protein that binds to metabotropic glutamate receptors via its FERM domain. Here, we determine the crystal structure of the FERM domain of FRMPD4 at 2.49 A resolution. The structure reveals that the canonical target binding groove of FRMPD4 FERM is occupied by a conserved fragment C-terminal to the FERM domain, suggesting that the FRMPD4-mGluR interaction may adopt a distinct binding mode. In addition, FRMPD4 FERM does not contain a typical phosphoinositide binding site at the F1/F3 cleft found in ERM family FERM domains, but it possesses a conserved basic residue cluster on the F2 lobe which could bind to lipid effectively. Finally, analysis of mutations that are associated with X-linked intellectual disability suggests that they may compromise the biological function of FRMPD4 by destabilizing the FERM structure.

Structure of the FERM domain of a neural scaffold protein FRMPD4 implicated in X-linked intellectual disability.,Wang M, Lin L, Shi Y, He L, Wang C, Zhu J Biochem J. 2020 Dec 11;477(23):4623-4634. doi: 10.1042/BCJ20200857. PMID:33216857^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.