TY - JOUR
T1 - Structure and function of virion RNA polymerase of a crAss-like phage
AU - Drobysheva, Arina V.
AU - Panafidina, Sofia A.
AU - Kolesnik, Matvei V.
AU - Klimuk, Evgeny I.
AU - Minakhin, Leonid
AU - Yakunina, Maria V.
AU - Borukhov, Sergei
AU - Nilsson, Emelie
AU - Holmfeldt, Karin
AU - Yutin, Natalya
AU - Makarova, Kira S.
AU - Koonin, Eugene V.
AU - Severinov, Konstantin V.
AU - Leiman, Petr G.
AU - Sokolova, Maria L.
N1 - Publisher Copyright: © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/1/14
Y1 - 2021/1/14
N2 - CrAss-like phages are a recently described expansive group of viruses that includes the most abundant virus in the human gut1–3. The genomes of all crAss-like phages encode a large virion-packaged protein2,4 that contains a DFDxD sequence motif, which forms the catalytic site in cellular multisubunit RNA polymerases (RNAPs)5. Here, using Cellulophaga baltica crAss-like phage phi14:2 as a model system, we show that this protein is a DNA-dependent RNAP that is translocated into the host cell along with the phage DNA and transcribes early phage genes. We determined the crystal structure of this 2,180-residue enzyme in a self-inhibited state, which probably occurs before virion packaging. This conformation is attained with the help of a cleft-blocking domain that interacts with the active site and occupies the cavity in which the RNA–DNA hybrid binds. Structurally, phi14:2 RNAP is most similar to eukaryotic RNAPs that are involved in RNA interference6,7, although most of the phi14:2 RNAP structure (nearly 1,600 residues) maps to a new region of the protein fold space. Considering this structural similarity, we propose that eukaryal RNA interference polymerases have their origins in phage, which parallels the emergence of the mitochondrial transcription apparatus8.
AB - CrAss-like phages are a recently described expansive group of viruses that includes the most abundant virus in the human gut1–3. The genomes of all crAss-like phages encode a large virion-packaged protein2,4 that contains a DFDxD sequence motif, which forms the catalytic site in cellular multisubunit RNA polymerases (RNAPs)5. Here, using Cellulophaga baltica crAss-like phage phi14:2 as a model system, we show that this protein is a DNA-dependent RNAP that is translocated into the host cell along with the phage DNA and transcribes early phage genes. We determined the crystal structure of this 2,180-residue enzyme in a self-inhibited state, which probably occurs before virion packaging. This conformation is attained with the help of a cleft-blocking domain that interacts with the active site and occupies the cavity in which the RNA–DNA hybrid binds. Structurally, phi14:2 RNAP is most similar to eukaryotic RNAPs that are involved in RNA interference6,7, although most of the phi14:2 RNAP structure (nearly 1,600 residues) maps to a new region of the protein fold space. Considering this structural similarity, we propose that eukaryal RNA interference polymerases have their origins in phage, which parallels the emergence of the mitochondrial transcription apparatus8.
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U2 - 10.1038/s41586-020-2921-5
DO - 10.1038/s41586-020-2921-5
M3 - Article
C2 - 33208949
SN - 0028-0836
VL - 589
SP - 306
EP - 309
JO - Nature
JF - Nature
IS - 7841
ER -