Structural basisof basal pilin incorporation into the bacterial pilus fiber

Bacteria assemblevariety of hair-like surface organelles called pili or fimbriae on their surface for multiple purposes including adhesion, biofilm formation, immunomodulation, motility conjugation, and conducting electricity. Subtle differences in the pilus assembly and structure distinguish the bacterial strains and dictate tissue tropism and host specificity. Targeting pili and pili-mediated interaction appear to be a promising approach in combating infection and improving health. However, thesenanofibresare so small in size (~0.7nm diameter i.e. 100,000 times smaller than the width of a human hair) and havecomplex architecture made of different building blocks called pilins. Unlike other pilus types, the sortase-dependent (SD) pili found only in Gram-positive bacteria are relatively thinner yet stronger. The stability and resistant to mechanical stress and degradation ofthe SD pili mainly comes from molecular weldings (isopeptide bonds) between and within the blocks. The SD pili are made up of three different building blocks (tip, backbone and basal pilins). Dr. Krishnan’s structural biology group at RCB has begun to visualize individual building blocks of probiotic L. rhamnosus GG at a high resolution (atomic scale) using X-ray crystallography towards understanding pilus biogenesis and architecture. They have previously obtained structure of backbone blocks and proposed a mechanism called ‘expose-ligate-seal’ by which pilus backbone or shaft is assembled (Comm. Biol. 1: 94,2018 ;Sci. Rep. 6:28664, 2016). They have now discovered three-dimensional shape of basal unit at a very high resolution and show how it is incorporated into the pilus fiber. The first atomic structure of basal blockfrom a commensal bacteriumshows two parts (head and tail). Its head part is similar to that of backbone block with internal isopeptide bonds.The head of the basal block is complementary to the shape of the tail part of backbone block with the exposed welding pointwhichreadily allows it to dock into the growing pilus fiber andto form inter-blockswelding for terminating the pilus growth.

Megta AK, Mishra AK, Palva A, von Ossowski I, Krishnan V (2019) Crystal structure of basal pilin SpaE reveals the molecular basis of its incorporation in the lactobacillar SpaFED pilus. J Struct Biol | Doi: 10.1016/j.jsb.2019.04.016.

Structural insights into the minimum viable pilus

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