7BYJ

Crystal structure of the FERM domain of FRMPD4

Summary for 7BYJ

• Entry DOI: 10.2210/pdb7byj/pdb
• Descriptor: FERM and PDZ domain-containing protein 4 (2 entities in total)
• Functional Keywords: ferm, frmpd4, neural scaffold protein, protein binding
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 38562.95

Authors

Lin, L.,Wang, M.,Wang, C.,Zhu, J. (deposition date: 2020-04-23, release date: 2020-12-16, Last modification date: 2024-10-09)

Primary citation

Wang, M.,Lin, L.,Shi, Y.,He, L.,Wang, C.,Zhu, J.
Structure of the FERM domain of a neural scaffold protein FRMPD4 implicated in X-linked intellectual disability.
Biochem.J., 477:4623-4634, 2020

PubMed Abstract: 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 Å 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.

PubMed: 33216857
DOI: 10.1042/BCJ20200857

Experimental method

X-RAY DIFFRACTION (2.49 Å)