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Bacterial effectors mediate kinase reprogramming through a series of evolutionary conserved amino acids that mimic eukaryotic motifs

ABSTRACT: Bacteria have evolved numerous biochemical processes that underpin their biology and pathogenesis. The small, non-enzymatic bacterial (Salmonella) effector SteE mediates kinase reprogramming, whereby the canonical serine/threonine host kinase GSK3 gains tyrosine-directed activity towards neosubstrates, promoting Salmonella virulence. Yet, both the mechanism behind the switch in GSK3’s activity and the diversity of this phenomenon remain to be determined. Here we show that kinase reprogramming of GSK3 is mediated by putative homologues from diverse Gram-negative pathogens. Next, we identify both the molecular basis of how SteE targets GSK3 and then uncover that the SteE-induced tyrosine activity conferred on GSK3 occurs by mimicry of an L/xGxP motif, previously shown to mediate GSK3 autophosphorylation on a tyrosine. Together, we demonstrate how a family of intrinsically disordered proteins mediate kinase reprogramming through the molecular mimicry of eukaryotic short linear motifs. With these advances comes the potential for the rationale design of synthetic reprogramming proteins

INSTRUMENT(S):

ORGANISM(S): Salmonella Sp. Wt

TISSUE(S): Cell Culture

SUBMITTER: Sarah Maslen

LAB HEAD: Dr. Katrin Rittinger

PROVIDER: PXD058368 | Pride | 2025-04-25

REPOSITORIES: Pride

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			Action	DRS
	GSK3B_State.csv	Csv
	GSK3B_SteE.zip	Other
	SteE_State.csv	Csv

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