Structural Cues for Understanding eEF1A2 Moonlighting.
Chembiochem
; 22(2): 374-391, 2021 01 15.
Article
in English
| MEDLINE | ID: covidwho-739622
ABSTRACT
Spontaneous mutations in the EEF1A2 gene cause epilepsy and severe neurological disabilities in children. The crystal structure of eEF1A2 protein purified from rabbit skeletal muscle reveals a post-translationally modified dimer that provides information about the sites of interaction with numerous binding partners, including itself, and maps these mutations onto the dimer and tetramer interfaces. The spatial locations of the side chain carboxylates of Glu301 and Glu374, to which phosphatidylethanolamine is uniquely attached via an amide bond, define the anchoring points of eEF1A2 to cellular membranes and interorganellar membrane contact sites. Additional bioinformatic and molecular modeling results provide novel structural insight into the demonstrated binding of eEF1A2 to SH3 domains, the common MAPK docking groove, filamentous actin, and phosphatidylinositol-4 kinase IIIß. In this new light, the role of eEF1A2 as an ancient, multifaceted, and articulated G protein at the crossroads of autophagy, oncogenesis and viral replication appears very distant from the "canonical" one of delivering aminoacyl-tRNAs to the ribosome that has dominated the scene and much of the thinking for many decades.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Peptide Elongation Factor 1
Limits:
Humans
Language:
English
Journal:
Chembiochem
Journal subject:
Biochemistry
Year:
2021
Document Type:
Article
Affiliation country:
Cbic.202000516
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