Structures of kobuviral and siciniviral polymerases reveal conserved mechanism of picornaviral polymerase activation

0511491 - ÚOCHB 2020 RIV US eng J - Journal Article
Dubánková, Anna - Horová, Vladimíra - Klíma, Martin - Bouřa, Evžen
Structures of kobuviral and siciniviral polymerases reveal conserved mechanism of picornaviral polymerase activation.
Journal of Structural Biology. Roč. 208, č. 2 (2019), s. 92-98. ISSN 1047-8477. E-ISSN 1095-8657
R&D Projects: GA MŠMT(CZ) EF16_019/0000729; GA ČR(CZ) GJ17-07058Y
Institutional support: RVO:61388963
Keywords : RNA * polymerase * crystal structure * kobuvirus * picornavirus
OECD category: Biochemistry and molecular biology
Impact factor: 3.071, year: 2019
Method of publishing: Limited access
https://www.sciencedirect.com/science/article/pii/S1047847719301741?via%3Dihub

RNA-dependent RNA polymerase 3D(pol) is a key enzyme for the replication of picomaviruses. The viral genome is translated into a single polyprotein that is subsequently proteolytically processed into matured products. The 3D(pol )enzyme arises from a stable 3CD precursor that has high proteolytic activity but no polymerase activity. Upon cleavage of the precursor the newly established N-terminus of 3D(pol) I is liberated and inserts itself into a pocket on the surface of the 3D(pol) enzyme. The essential residue for this mechanism is the very first glycine that is conserved among almost all picomaviruses. However, kobuviruses and siciniviruses have a serine residue instead. Intrigued by this anomaly we sought to solve the crystal structure of these 3D(pol) enzymes. The structures revealed a unique fold of the 3D(pol) N-termini but the very first serine residues were inserted into a charged pocket in a similar manner as the glycine residue in other picomaviruses. These structures revealed a common underlying mechanism of 3D(pol) activation that lies in activation of the alpha 10 helix containing a key catalytical residue Asp238 that forms a hydrogen bond with the 2' hydroxyl group of the incoming NTP nucleotide.
Permanent Link: http://hdl.handle.net/11104/0301739