An essential and highly selective protein import pathway encoded by nucleus-forming phage
[1];
[1];
[2];
[1];
[1];
[3];
[4];
[5];
[1];
[1];
- Univ. of California San Diego, La Jolla, CA (United States)
- Univ. of California San Diego, La Jolla, CA (United States); Chulalongkorn Univ., Bangkok (Thailand)
- Chulalongkorn Univ., Bangkok (Thailand)
- Univ. of California, Berkeley, CA (United States)
- Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
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.
- Research Organization:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); USDOE
- Grant/Contract Number:
- AC02-05CH11231; R01-GM129245; R35 GM144121; GM133351; InCoGenTEC
- OSTI ID:
- 2342165
- Alternate ID(s):
- OSTI ID: 2407020
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America, Vol. 121, Issue 19; ISSN 0027-8424
- Publisher:
- National Academy of SciencesCopyright Statement
- Country of Publication:
- United States
- Language:
- English
Similar Records
Systematic and scalable genome-wide essentiality mapping to identify nonessential genes in phages
Effects of PQ's cytotoxicity on secretory vesicles in astroglia: Expression alternation of secretogranin II and its potential interaction with intracellular factors