The BID Domain of Type IV Secretion Substrates Forms a Conserved Four-Helix Bundle Topped with a Hook

Stanger, Frédéric V.; Beer, Tjaart de; Dranow, David M.; Schirmer, Tilman; Phan, Isabelle; Dehio, Christoph

doi:10.1016/j.str.2016.10.010

Cited by 21 publications

(49 citation statements)

References 23 publications

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“…Functional annotation of these atypical poly‐Ubs on BepE requires further investigation. Previous study showed amino acid composition of BID domains from different Beps is not well conserved (Stanger et al, ). We also found that lysine residue at site of 365 of Bqu ‐BepE is not identical among BepE orthologues.…”

Section: Discussionmentioning

confidence: 96%

Bartonella quintana type IV secretion effector BepE ‐induced selective autophagy by conjugation with K63 polyubiquitin chain

Wang

et al. 2018

Cellular Microbiology

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Bartonella effector proteins (named Beps) are substrates of VirB type IV secretion system for translocation into host cells evolved in Bartonella spp. Among these, BepE has been shown to protect cells from fragmentation effects triggered by other Beps and to promote in vivo dissemination of bacteria from the dermal site of inoculation to the bloodstream. Bacterial pathogens secreted effectors to modulate the interplay with host autophagy, either to combat autophagy to escape its bactericidal effect or to exploit autophagy to benefit intracellular replication. Here, we reported a distinct phenotype that selective autophagy in host cells is activated as a countermeasure, to attack BepE via conjugation with K63 polyubiquitin chain on BepE. We found that ectopic expression of Bartonella quintana BepE specifically induced punctate structures that colocalised with an autophagy marker (LC3‐II) in host cells, in addition to filopodia and membrane ruffle formation. Two tandemly arranged Bartonella Intracellular Delivery (BID) domains in the BepE C‐terminus, where ubiquitination of sister pairs of lysine residues was confirmed, were essential to activate host cell autophagy. Multiple polyubiquitin chain linkages of K27, K29, K33, and K63 were found to be conjugated at sites of K222 and K365 on BepE, of which K63 polyubiquitination on BepE K365 determined the selective autophagy (p62/SQSTM1 positive autophagy) independent of the PI3K pathway. Colocalisation of BepE with LAMP1 confirmed the maturation of BepE‐induced autophagosomes in which BepE were targeted for degradation. Moreover, host cells employed selective autophagy to counter‐attack BepE to rescue cells from BepE‐induced endocytosis deficiency.

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Section: Discussionmentioning

confidence: 96%

Bartonella quintana type IV secretion effector BepE ‐induced selective autophagy by conjugation with K63 polyubiquitin chain

Wang

et al. 2018

Cellular Microbiology

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“…On the basis of the solved BID domain structures, the conserved overall fold suggests a crucial role in initial steps of T4SS mediated Bep translocation into host cells. In contrast, the less conserved surface of BID domains seems to have facilitated the evolution of new interaction interfaces with host target proteins, thereby modulating different cellular pathways (Stanger et al, ). We further believe that the high degree of surface variability of BID domains of Bep orthologues might display an adaptive step to fine‐tune host‐restricted interactions.…”

Section: Parallel Evolution Of Complex Bep Repertoiresmentioning

confidence: 99%

Role of distinct type‐IV‐secretion systems and secreted effector sets in host adaptation by pathogenicBartonellaspecies

Wagner

Dehio

2019

Cellular Microbiology

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The α‐proteobacterial genus Bartonella comprises a large number of facultative intracellular pathogens that share a common lifestyle hallmarked by hemotrophic infection and arthropod transmission. Speciation in the four deep‐branching lineages (L1–L4) occurred by host adaptation facilitating the establishment of long lasting bacteraemia in specific mammalian reservoir host(s). Two distinct type‐IV‐secretion systems (T4SSs) acquired horizontally by different Bartonella lineages mediate essential host interactions during infection and represent key innovations for host adaptation. The Trw‐T4SS confined to the species‐rich L4 mediates host‐specific erythrocyte infection and likely has functionally replaced flagella as ancestral virulence factors implicated in erythrocyte colonisation by bartonellae of the other lineages. The VirB/VirD4‐T4SS translocates Bartonella effector proteins (Bep) into various host cell types to modulate diverse cellular and innate immune functions involved in systemic spreading of bacteria following intradermal inoculation. Independent acquisition of the virB/virD4/bep locus by L1, L3, and L4 was likely driven by arthropod vectors associated with intradermal inoculation of bacteria rather than facilitating direct access to blood. Subsequently, adaptation to colonise specific niches in the new host has shaped the evolution of complex species‐specific Bep repertoires. This diversification of the virulence factor repertoire of Bartonella spp. represents a remarkable example for parallel evolution of host adaptation.

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“…A comparison of SgEsaA235-829 to previously determined structures in the Protein Data Bank using DALILITE revealed that the overall structure of SgEsaA235-829 does not resemble proteins of known structure (Holm, 2020). The top hit from this search was the BID domain of the type IV secretion system (T4SS) effector protein Bep9 from Bartonella clarridgeiae (Zscore, 8.5; Ca root mean square deviation of 3.5Å over 100 aligned residues), which only shares structural similarity with AD-I of EsaA ( Figure S3) (Stanger et al, 2017). BID domains comprise one part of a bipartite signal sequence found in some T4SS effectors and thus appear unrelated in terms of function.…”

Section: Esaa Forms An Elongated Arrow-shaped Dimermentioning

confidence: 99%

Structure of the extracellular region of the bacterial type VIIb secretion system subunit EsaA

Klein

Grebenc

Gandhi

et al. 2020

Preprint

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Gram-positive bacteria use type VII secretion systems (T7SSs) to export effector proteins that manipulate the physiology of nearby prokaryotic and eukaryotic cells. Several mycobacterial T7SSs have established roles in virulence. By contrast, recent work has demonstrated that the genetically distinct T7SSb pathway found in Firmicutes bacteria more often functions to mediate interbacterial competition. A lack of structural information on the T7SSb has limited the understanding of effector export by this protein secretion apparatus. In this work, we present the 2.4Å crystal structure of the extracellular region of the elusive T7SSb subunit EsaA from Streptococcus gallolyticus. Our structure reveals that homodimeric EsaA is an elongated, arrow-shaped protein with a surface-accessible ′tip′, which serves as a receptor for lytic bacteriophages in some species of bacteria. Because it is the only T7SSb subunit large enough to traverse the thick peptidoglycan layer of Firmicutes bacteria, we propose that EsaA plays a critical role in transporting effectors across the entirety of the Gram-positive cell envelope.

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The BID Domain of Type IV Secretion Substrates Forms a Conserved Four-Helix Bundle Topped with a Hook

Cited by 21 publications

References 23 publications

Bartonella quintana type IV secretion effector BepE ‐induced selective autophagy by conjugation with K63 polyubiquitin chain

Bartonella quintana type IV secretion effector BepE ‐induced selective autophagy by conjugation with K63 polyubiquitin chain

Role of distinct type‐IV‐secretion systems and secreted effector sets in host adaptation by pathogenicBartonellaspecies

Structure of the extracellular region of the bacterial type VIIb secretion system subunit EsaA

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