Structural highlights
Function
[K3_VACCW] Viral mimic of eIF-2-alpha that acts as a pseudosubstrate for EIF2AK2/PKR kinase. Inhibits therefore eIF-2-alpha phosphorylation by host EIF2AK2/PKR kinase and prevents protein synthesis shutoff.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The vaccinia virus protein K3L subverts the mammalian antiviral defense mechanism by inhibiting the RNA-dependent protein kinase PKR. K3L is a structural mimic of PKR's natural substrate, the translation initiation factor eIF2alpha. To further our understanding of K3L inhibitory function and PKR substrate recognition, we have solved the 1.8 A X-ray crystal structure of K3L. The structure consists of a five-strand beta barrel with an intervening helix insert region similar in topology to the functionally divergent S1 domain. Mutational analysis identifies two proximal regions of the K3L structure as possessing specialized PKR binding and inhibitory function. Further analysis reveals that PKR dimerization composes a key switch that regulates both its catalytic activation and its molecular recognition of K3L and eIF2alpha.
X-ray crystal structure and functional analysis of vaccinia virus K3L reveals molecular determinants for PKR subversion and substrate recognition.,Dar AC, Sicheri F Mol Cell. 2002 Aug;10(2):295-305. PMID:12191475[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Carroll K, Elroy-Stein O, Moss B, Jagus R. Recombinant vaccinia virus K3L gene product prevents activation of double-stranded RNA-dependent, initiation factor 2 alpha-specific protein kinase. J Biol Chem. 1993 Jun 15;268(17):12837-42. PMID:8099586
- ↑ Dar AC, Sicheri F. X-ray crystal structure and functional analysis of vaccinia virus K3L reveals molecular determinants for PKR subversion and substrate recognition. Mol Cell. 2002 Aug;10(2):295-305. PMID:12191475
