RT Journal Article SR Electronic T1 Dormant spores sense amino acids through the B subunits of their germination receptors JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.10.28.466322 DO 10.1101/2021.10.28.466322 A1 Lior Artzi A1 Assaf Alon A1 Kelly P. Brock A1 Anna G. Green A1 Amy Tam A1 Fernando H. Ramírez-Guadiana A1 Debora Marks A1 Andrew Kruse A1 David Z. Rudner YR 2021 UL http://biorxiv.org/content/early/2021/10/28/2021.10.28.466322.abstract AB Bacteria from the orders Bacillales and Clostridiales differentiate into stress-resistant spores that can remain dormant for years, yet rapidly germinate upon nutrient sensing. How spores monitor nutrients is poorly understood but in most cases requires putative membrane receptors. The prototypical receptor from Bacillus subtilis consists of three proteins (GerAA, GerAB, GerAC) required for germination in response to L-alanine. GerAB belongs to the Amino Acid-Polyamine-Organocation superfamily of transporters. Using evolutionary co-variation analysis, we provide evidence that GerAB adopts a structure similar to an L-alanine transporter from this superfamily. We show that mutations in gerAB predicted to disrupt the ligand-binding pocket impair germination, while mutations predicted to function in L-alanine recognition enable spores to respond to L-leucine or L-serine. Finally, substitutions of bulkier residues at these positions cause constitutive germination. These data suggest that GerAB is the L-alanine sensor and that B subunits in this broadly conserved family function in nutrient detection.Competing Interest StatementThe authors have declared no competing interest.