1887

Abstract

569 spores germinate either with inosine as a sole germinant or with a combination of nucleosides and -alanine. Whereas the inosine-only germination pathway requires the presence of two different germination receptors (GerI and GerQ) to be activated, the nucleoside/alanine germination pathway only needs one of the two receptors. To differentiate how nucleoside recognition varies between the inosine-only germination pathway and the nucleoside/alanine germination pathway, we tested 61 purine analogues as agonists and antagonists of the two pathways in wild-type, Δ and Δ spores. The structure–activity relationships of germination agonists and antagonists suggest that the inosine-only germination pathway is restricted to recognize a single germinant (inosine), but can be inhibited in predictable patterns by structurally distinct purine nucleosides. spores encoding GerI as the only nucleoside receptor (Δ mutant) showed a germination inhibition profile similar to wild-type spores treated with inosine only. Thus, GerI seems to have a well-organized binding site that recognizes inosine and inhibitors through specific substrate–protein interactions. Structure–activity analysis also showed that the nucleoside/alanine germination pathway is more promiscuous toward purine nucleoside agonists, and is only inhibited by hydrophobic analogues. spores encoding GerQ as the only nucleoside receptor (Δ mutant) behaved like wild-type spores treated with inosine and -alanine. Thus, the GerQ receptor seems to recognize substrates in a more flexible binding site through non-specific interactions. We propose that the GerI receptor is responsible for germinant detection in the inosine-only germination pathway. On the other hand, supplementing inosine with -alanine allows bypassing of the GerI receptor to activate the more flexible GerQ receptor.

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2010-04-01
2020-07-04
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