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Conserved structural mechanisms for autoinhibition in IpaH ubiquitin ligases.

ABSTRACT: The IpaH family of novel E3 ligase (NEL) enzymes occur in a variety of pathogenic and commensal bacteria that interact with eukaryotic hosts. We demonstrate that the leucine-rich repeat (LRR) substrate recognition domains of different IpaH enzymes autoinhibit the enzymatic activity of the adjacent catalytic novel E3 ligase domain by two distinct but conserved structural mechanisms. Autoinhibition is required for the in vivo biological activity of two IpaH enzymes in a eukaryotic model system. Autoinhibition was retro-engineered into a constitutively active IpaH enzyme from Yersinia pestis by introduction of single site substitutions, thereby demonstrating the conservation of autoregulatory infrastructure across the IpaH enzyme family.

SUBMITTER: Chou YC

PROVIDER: S-EPMC3249077 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Conserved structural mechanisms for autoinhibition in IpaH ubiquitin ligases.

Chou Yang-Chieh YC Keszei Alexander F A AFA Rohde John R JR Tyers Mike M Sicheri Frank F

The Journal of biological chemistry 20111107 1

The IpaH family of novel E3 ligase (NEL) enzymes occur in a variety of pathogenic and commensal bacteria that interact with eukaryotic hosts. We demonstrate that the leucine-rich repeat (LRR) substrate recognition domains of different IpaH enzymes autoinhibit the enzymatic activity of the adjacent catalytic novel E3 ligase domain by two distinct but conserved structural mechanisms. Autoinhibition is required for the in vivo biological activity of two IpaH enzymes in a eukaryotic model system. Au ...[more]

PMID: 22065585

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