Little Janay I, Singh Pradip Kumar, Samsó Montserrat, Donnenberg Michael S
School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Pathogens. 2025 May 13;14(5):471. doi: 10.3390/pathogens14050471.
Type IV pili (T4Ps) are multifunctional surface fibers essential for bacterial motility, adhesion, and virulence, found across Gram-negative and Gram-positive bacteria and archaea. Detailed descriptions of T4P structural biology are allowing progress in understanding T4P biogenesis. Secretins, large outer membrane channels, are crucial for T4P extrusion in Gram-negative bacteria. Using cryo-EM and AlphaFold, we modeled the structure of BfpB, the secretin of the Bundle-Forming Pilus (BFP) of enteropathogenic . BfpB exhibits a unique 17-fold symmetry, correlating with the thicker BFP filaments, and diverging from the 12-15 subunits typical of T4P, type 2 secretion (T2S), and type 3 secretion (T3S) systems. Additionally, we identified an extended β-hairpin loop in the N3 domain, resembling features of distantly related T3SS secretins, and an N-terminal helix where a C-terminal S-domain is seen in some T2S and T3S secretins. These findings reveal evolutionary parallels and structural adaptations in secretins, highlighting the link between oligomerization and pilus structure. This work advances our understanding of T4P biogenesis, secretin evolution, and bacterial secretion systems, offering insights into pathogenic diversity and future research directions.
IV型菌毛（T4P）是多功能表面纤维，对细菌的运动、黏附和毒力至关重要，存在于革兰氏阴性菌、革兰氏阳性菌和古菌中。对T4P结构生物学的详细描述有助于深入了解T4P的生物合成过程。分泌素是一种大型外膜通道，对革兰氏阴性菌中T4P的挤出至关重要。我们利用冷冻电镜和AlphaFold对肠道致病性大肠杆菌束状菌毛（BFP）的分泌素BfpB的结构进行了建模。BfpB呈现出独特的17倍对称性，这与更粗的BFP细丝相关，并且不同于T4P、2型分泌（T2S）和3型分泌（T3S）系统典型的12 - 15个亚基。此外，我们在N3结构域中发现了一个延伸的β-发夹环，类似于远亲T3SS分泌素的特征，以及一个N端螺旋，在一些T2S和T3S分泌素中可以看到其C端S结构域。这些发现揭示了分泌素在进化上的相似性和结构适应性，突出了寡聚化与菌毛结构之间的联系。这项工作增进了我们对T4P生物合成、分泌素进化和细菌分泌系统的理解，为致病性多样性和未来研究方向提供了见解。
