An essential and highly selective protein import pathway encoded by nucleus-forming phage.

Autor:	Morgan CJ; School of Biological Sciences, Division of Molecular Biology, University of California San Diego, La Jolla, CA 92093., Enustun E; School of Biological Sciences, Division of Molecular Biology, University of California San Diego, La Jolla, CA 92093., Armbruster EG; School of Biological Sciences, Division of Molecular Biology, University of California San Diego, La Jolla, CA 92093., Birkholz EA; School of Biological Sciences, Division of Molecular Biology, University of California San Diego, La Jolla, CA 92093., Prichard A; School of Biological Sciences, Division of Molecular Biology, University of California San Diego, La Jolla, CA 92093., Forman T; School of Biological Sciences, Division of Molecular Biology, University of California San Diego, La Jolla, CA 92093., Aindow A; School of Biological Sciences, Division of Molecular Biology, University of California San Diego, La Jolla, CA 92093., Wannasrichan W; School of Biological Sciences, Division of Molecular Biology, University of California San Diego, La Jolla, CA 92093.; Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand 10330., Peters S; School of Biological Sciences, Division of Molecular Biology, University of California San Diego, La Jolla, CA 92093., Inlow K; School of Biological Sciences, Division of Molecular Biology, University of California San Diego, La Jolla, CA 92093., Shepherd IL; School of Biological Sciences, Division of Molecular Biology, University of California San Diego, La Jolla, CA 92093., Razavilar A; School of Biological Sciences, Division of Molecular Biology, University of California San Diego, La Jolla, CA 92093., Chaikeeratisak V; Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand 10330., Adler BA; California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720.; Innovative Genomics Institute, University of California, Berkeley, CA 94720.; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720., Cress BF; Innovative Genomics Institute, University of California, Berkeley, CA 94720.; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720., Doudna JA; California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720.; Innovative Genomics Institute, University of California, Berkeley, CA 94720.; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720.; Department of Chemistry, University of California, Berkeley, CA 94720.; HHMI, University of California, Berkeley, CA 94720.; Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720.; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720., Pogliano K; School of Biological Sciences, Division of Molecular Biology, University of California San Diego, La Jolla, CA 92093., Villa E; School of Biological Sciences, Division of Molecular Biology, University of California San Diego, La Jolla, CA 92093.; HHMI, University of California San Diego, La Jolla, CA 92093., Corbett KD; School of Biological Sciences, Division of Molecular Biology, University of California San Diego, La Jolla, CA 92093.; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093., Pogliano J; School of Biological Sciences, Division of Molecular Biology, University of California San Diego, La Jolla, CA 92093.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 May 07; Vol. 121 (19), pp. e2321190121. Date of Electronic Publication: 2024 Apr 30.
DOI:	10.1073/pnas.2321190121
Abstrakt:	Targeting proteins to specific subcellular destinations is essential in prokaryotes, eukaryotes, and the viruses that infect them. Chimalliviridae phages encapsulate their genomes in a nucleus-like replication compartment composed of the protein chimallin (ChmA) that excludes ribosomes and decouples transcription from translation. These phages selectively partition proteins between the phage nucleus and the bacterial cytoplasm. Currently, the genes and signals that govern selective protein import into the phage nucleus are unknown. Here, we identify two components of this protein import pathway: a species-specific surface-exposed region of a phage intranuclear protein required for nuclear entry and a conserved protein, PicA (Protein importer of chimalliviruses A), that facilitates cargo protein trafficking across the phage nuclear shell. We also identify a defective cargo protein that is targeted to PicA on the nuclear periphery but fails to enter the nucleus, providing insight into the mechanism of nuclear protein trafficking. Using CRISPRi-ART protein expression knockdown of PicA, we show that PicA is essential early in the chimallivirus replication cycle. Together, our results allow us to propose a multistep model for the Protein Import Chimallivirus pathway, where proteins are targeted to PicA by amino acids on their surface and then licensed by PicA for nuclear entry. The divergence in the selectivity of this pathway between closely related chimalliviruses implicates its role as a key player in the evolutionary arms race between competing phages and their hosts. Competing Interests: Competing interests statement:K.P. and J.P. have an equity interest in Linnaeus Bioscience Incorporated and receive income. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict-of-interest policies. J.A.D. is a cofounder of Caribou Biosciences, Editas Medicine, Scribe Therapeutics, Intellia Therapeutics, and Mammoth Biosciences. J.A.D. is a scientific advisory board member of Vertex, Caribou Biosciences, Intellia Therapeutics, Scribe Therapeutics, Mammoth Biosciences, Algen Biotechnologies, Felix Biosciences, The Column Group, and Inari. J.A.D. is Chief Science Advisor to Sixth Street, a Director at Johnson & Johnson, Altos and Tempus, and has research projects sponsored by Apple Tree Partners and Roche. The Regents of the University of California have patents issued and pending for CRISPR technologies on which J.A.D., B.F.C., B.A.A., J.P., K.P., and E.G.A. are inventors.
Databáze:	MEDLINE
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