3QD2

Crystal structure of mouse PERK kinase domain

Summary for 3QD2

• Entry DOI: 10.2210/pdb3qd2/pdb
• Descriptor: Eukaryotic translation initiation factor 2-alpha kinase 3 (2 entities in total)
• Functional Keywords: eif2a kinase, phosphoryalation, gene regulation
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 1
• Total formula weight: 38670.22

Authors

Wenjun, C.,Jingzhi, L.,David, R.,Bingdong, S. (deposition date: 2011-01-17, release date: 2011-04-27, Last modification date: 2024-11-20)

Primary citation

Cui, W.,Li, J.,Ron, D.,Sha, B.
The structure of the PERK kinase domain suggests the mechanism for its activation.
Acta Crystallogr.,Sect.D, 67:423-428, 2011

PubMed Abstract: The endoplasmic reticulum (ER) unfolded protein response (UPR) is comprised of several intracellular signaling pathways that alleviate ER stress. The ER-localized transmembrane kinase PERK is one of three major ER stress transducers. Oligomerization of PERK's N-terminal ER luminal domain by ER stress promotes PERK trans-autophosphorylation of the C-terminal cytoplasmic kinase domain at multiple residues including Thr980 on the kinase activation loop. Activated PERK phosphorylates Ser51 of the α-subunit of translation initiation factor 2 (eIF2α), which inhibits initiation of protein synthesis and reduces the load of unfolded proteins entering the ER. The crystal structure of PERK's kinase domain has been determined to 2.8 Å resolution. The structure resembles the back-to-back dimer observed in the related eIF2α kinase PKR. Phosphorylation of Thr980 stabilizes both the activation loop and helix αG in the C-terminal lobe, preparing the latter for eIF2α binding. The structure suggests conservation in the mode of activation of eIF2α kinases and is consistent with a `line-up' model for PERK activation triggered by oligomerization of its luminal domain.

PubMed: 21543844
DOI: 10.1107/S0907444911006445

Experimental method

X-RAY DIFFRACTION (2.81 Å)