7E2K

Crystal structure of the RWD domain of human GCN2 - 1

Summary for 7E2K

• Entry DOI: 10.2210/pdb7e2k/pdb
• Descriptor: eIF-2-alpha kinase GCN2 (2 entities in total)
• Functional Keywords: activator, kinase, rna-binding, serine/threonine-protein kinase, transferase, trna-binding
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 15301.24

Authors

Hei, Z.,Zhou, J.,Liu, Z.,Wang, J.,Fang, P. (deposition date: 2021-02-05, release date: 2021-03-17, Last modification date: 2023-11-29)

Primary citation

Hei, Z.,Wu, S.,Zheng, L.,Zhou, J.,Liu, Z.,Wang, J.,Fang, P.
Crystal structures reveal a novel dimer of the RWD domain of human general control nonderepressible 2.
Biochem.Biophys.Res.Commun., 549:164-170, 2021

PubMed Abstract: General control nonderepressible 2 (GCN2) is a serine/threonine protein kinase, detecting a variety of stresses including amino acid starvation, reactive oxygen species, etc. in eukaryotic cells. Activation of GCN2 requires the interaction of the N-terminal RWD domain with the upstream GCN1 protein and the dimerization by the kinase domain. In this study, we determined two crystal structures of the RWD domain of human GCN2 in two different crystal packing modes. These two different crystal structures reveal a same dimer of the RWD domain, which has not been reported in previous studies. We further confirmed this novel dimer interaction in solution using gel filtration experiments, and in human embryonic kidney (HEK) 293 cells using bimolecular fluorescence complementation (BiFC) and co-immunoprecipitation (co-IP) assays. Together, this study discovers a potential protein-protein interface on the RWD domain of human GCN2, and suggests a possible regulation between the interaction of GCN1 and the formation of GCN2 dimer.

PubMed: 33676185
DOI: 10.1016/j.bbrc.2021.02.111

Experimental method

X-RAY DIFFRACTION (2.041 Å)