Structure of the FERM domain of a neural scaffold protein FRMPD4 implicated in X-linked intellectual disability.
Biochem J
; 477(23): 4623-4634, 2020 12 11.
Article
em En
| MEDLINE
| ID: mdl-33216857
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 2.49â
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos e Proteínas de Sinalização Intracelular
/
Genes Ligados ao Cromossomo X
/
Deficiência Intelectual
/
Mutação
Limite:
Humans
Idioma:
En
Revista:
Biochem J
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China