6gzs
From Proteopedia
Structure of Chlamydia trachomatis effector protein ChlaDUB1 bound to ubiquitin
Structural highlights
Function[CDUB1_CHLT2] Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protease possesses deubiquitinating and deneddylating activities (By similarity). Impairs ubiquitination and degradation of NF-kappa-B inhibitor alpha (NFKBIA), thereby preventing NF-kappa-B activation.[1] [UBB_HUMAN] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.[2] [3] Publication Abstract from PubMedPathogenic bacteria are armed with potent effector proteins that subvert host signalling processes during infection(1). The activities of bacterial effectors and their associated roles within the host cell are often poorly understood, particularly for Chlamydia trachomatis(2), a World Health Organization designated neglected disease pathogen. We identify and explain remarkable dual Lys63-deubiquitinase (DUB) and Lys-acetyltransferase activities in the Chlamydia effector ChlaDUB1. Crystal structures capturing intermediate stages of each reaction reveal how the same catalytic centre of ChlaDUB1 can facilitate such distinct processes, and enable the generation of mutations that uncouple the two activities. Targeted Chlamydia mutant strains allow us to link the DUB activity of ChlaDUB1 and the related, dedicated DUB ChlaDUB2 to fragmentation of the host Golgi apparatus, a key process in Chlamydia infection for which effectors have remained elusive. Our work illustrates the incredible versatility of bacterial effector proteins, and provides important insights towards understanding Chlamydia pathogenesis. A Chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation.,Pruneda JN, Bastidas RJ, Bertsoulaki E, Swatek KN, Santhanam B, Clague MJ, Valdivia RH, Urbe S, Komander D Nat Microbiol. 2018 Nov 5. pii: 10.1038/s41564-018-0271-y. doi:, 10.1038/s41564-018-0271-y. PMID:30397340[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Chlt2 | Human | Komander, D | Pruneda, J N | Acetyltransferase | Ce clan | Deubiquitinase | Enzyme | Hydrolase
