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Type 4 filaments (T4F) are a superfamily of versatile nanomachines, ubiquitous in prokaryotes, which use conserved multi-protein machineries to assemble and operate filamentous polymers of type 4 pilins. In the best-studied T4F, these machineries are complex, which has posed challenges to understanding the mechanisms of filament assembly and their multiple functions. Here, we report the systematic functional analysis of the Com pilus, a widespread T4F mediating DNA uptake during natural transformation in monoderm bacteria. Using Streptococcus sanguinis , we show that Com pili are bona fide type 4 pili (T4P), representing a new pilus sub-type. We show that with only eight components necessary for pilus assembly and functioning—all “core” proteins universally conserved in this superfamily—the Com pilus epitomizes a minimalistic T4F. We further demonstrate that core T4F components are sufficient for filament assembly. Paradoxically, akin to the more elaborate T4F, the Com pilus contains four minor pilins forming a complex, probably tip-located. Our results have global implications for T4F and make the Com pilus a model for elucidating fundamental processes underpinning filament assembly. Type 4 filaments (T4F) are nanomachines ubiquitous in prokaryotes, centered on filamentous polymers of type 4 pilins. T4F are exceptionally versatile and widespread virulence factors in bacterial pathogens. The mechanisms of filament assembly and the many functions they facilitate remain poorly understood because of the complexity of T4F machineries. This hinders the development of anti-T4F drugs. The significance of our research lies in characterizing the simplest known T4F—the Com pilus that mediates DNA uptake in competent monoderm bacteria—and showing that four protein components universally conserved in T4F are sufficient for filament assembly. The Com pilus becomes a model for elucidating the mechanisms of T4F assembly.

Bacteria are capable of evolving and diversifying very rapidly by acquiring new genetic material via horizontal gene transfer (HGT). Transformation is a widespread mechanism of HGT, which results from the capture of extracellular DNA by surface-exposed pili belonging to the type 4 filament (T4F) superfamily. How T4F—composed of major and minor pilins—interact with DNA remains poorly understood, especially in monoderm species that use a unique T4F for DNA capture, known as Com pilus or T4dP. The significance of this work is in characterizing a novel mode of DNA-binding by showing that the interface between two minor pilins, part of a tip-located complex of four pilins—found in different T4F—has been functionalized in monoderms to capture DNA. This is an evolutionary mechanism promoting the exceptional functional versatility of T4F.

Type 4 filaments (T4F) are a superfamily of functionally versatile nanomachines, ubiquitous in prokaryotes, which use similar multi-protein machineries to assemble and operate filamentous polymers of type 4 pilins. The best studied T4F use very complex machineries, which has posed challenges to understanding the mechanisms of both filament assembly and the roles they facilitate. Here, we report the systematic functional analysis of the Com pilus, a widespread T4F mediating DNA uptake during natural transformation in monoderm bacteria. Using Streptococcus sanguinis as a model, we show that Com pili are bona fide type 4 pili (T4P), which represent a new pilus sub-type. We show that with only eight components necessary for their assembly and functioning – all “core” poteins universally conserved across this superfamily – the Com pilus epitomises a minimalistic T4F. We demonstrate that core T4F components are sufficient for filament assembly. Intriguingly, akin to more elaborate T4F, the Com pilus contains four minor pilins forming a complex likely to be situated at the apex of the filaments. Our results have global implications for T4F and make Com pili a model for elucidating the fundamental processes underpinning filament assembly.

In loving memory of our loved one who passed away a year ago today, December 30, 1991. You always said you would be a millionaire by age 35; We just didn't know your wealth would be that of God's Kingdom. Give Timmy a hug for us. We miss you both.