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Evolutionarily Convergent Mechanism of Formin Regulation Coordinates Actin Polymerization in Apicomplexan Parasites

ABSTRACT: Apicomplexan parasites rely on actin-based motility for host cell invasion and for their dissemination. Although previous studies implicate formin 1 (FRM1) in governing this process in Toxoplasma, the mechanisms that position it at the cell apex and regulate its activity during the transition from intracellular replication to active motility remain unclear. Here, we demonstrate that FRM1 is complexed with a protein methyl transferase that stabilizes it from degradation and positions it at the cell apex. Moreover, we identify a conserved intramolecular interaction within FRM1 that serves as a critical regulatory switch that is functionally conserved in Plasmodium and other apicomplexan parasites. Using structural modeling combined with biochemical assays, we define two regulatory elements located upstream of the FH2 domain that mediate autoinhibition. Repositioning these elements by activation of an intramolecular switch relieves autoinhibition and activates actin polymerization by the FH2 domain. Collectively, these findings elucidate how precise regulation of FRM1 coordinates actin polymerization, parasite motility and host cell invasion.

INSTRUMENT(S):

ORGANISM(S): Toxoplasma Gondii Me49

TISSUE(S): Cell Culture

SUBMITTER: Sophe Alvarez

LAB HEAD: Michael Naldrett

PROVIDER: PXD068228 | Pride | 2025-11-04

REPOSITORIES: Pride

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			Action	DRS
	20250403_PQ_Bottom.raw	Raw
	20250403_PQ_Middle.raw	Raw
	20250404_PQ_Top.raw	Raw
	PQ_ProtID_Report_20250411_3mc_trimethylation_only.mzid.gz	Mzid
	PQ_ProtID_Report_20250411_3mc_trimethylation_only.mzid.gz_20250410_mascot_daemon_merge__F024703_.MGF	Mzid

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