Diverse ATPase proteins in mobilomes constitute a large potential sink for prokaryotic host ATP

TL;DR

This study reveals a high diversity and abundance of ATPase proteins in mobile genetic elements, suggesting they act as significant energy sinks and may influence host energy metabolism and immune interactions.

Contribution

It uncovers the extensive diversity and potential functional roles of ATPase proteins in mobilomes, highlighting their possible impact on host energy diversion and immune evasion strategies.

Findings

Up to 9% of proteins in huge phages have ATPase domains.

ATPase protein numbers increase linearly with genome length.

Many ATPase proteins are fused with domains involved in nucleic acid and protein interactions.

Abstract

Prokaryote mobilome genomes rely on host machineries for survival and replication. Given that mobile genetic elements (MGEs) derive their energy from host cells, we investigated the diversity of ATP-utilizing proteins in MGE genomes to determine whether they might be associated with proteins that could suppress related host proteins that consume host energy. A comprehensive search of 353 huge phage genomes revealed that up to 9% of the proteins have ATPase domains. For example, ATPase proteins constitute ~3% of the genomes of Lak phages with ~550 kbp genomes that occur in the microbiomes of humans and other animals. Statistical analysis shows the number of ATPase proteins increases linearly with genome length, consistent with a large sink for host ATP during replication of megaphages. Using metagenomic data from diverse environments, we found 505 mobilome proteins with ATPase domains fused to diverse functional domains. Among these composite ATPase proteins, 61.6% have known functional domains that could contribute to host energy diversion during the mobilome life cycle. As many have domains that are known to interact with nucleic acids and proteins, we infer that numerous ATPase proteins are used during replication and for protection from host immune systems. We found a set of uncharacterized ATPase proteins with nuclease and protease activities, displaying unique domain architectures that are energy intensive based on the presence of multiple ATPase domains. In many cases, these composite ATPase proteins genomically co-localize with small proteins in genomic contexts that are reminiscent of toxin-antitoxin systems. Small proteins that function as inhibitors may be a common strategy for control of cellular processes, thus could inspire the development of new nucleic acid and protein manipulation tools, with diverse biotechnological applications.