IcmQ in the Type 4b Secretion System Contains an NAD+ Binding Domain

Farelli, Jeremiah D.; Gumbart, James C.; Akey, Ildikó V.; Hempstead, Andrew D.; Amyot, Whitney; Head, James F.; McKnight, C. James; Isberg, Ralph R.; Akey, Christopher W.

doi:10.1016/j.str.2013.05.017

Cited by 6 publications

(8 citation statements)

References 57 publications

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“…S8, Supplementary Material online). The structure of full-length IcmQ in complex with IcmR revealed that the C-terminal domain of IcmQ contains a NAD + binding domain (Farelli et al. 2013).…”

Section: Resultsmentioning

confidence: 99%

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Evolutionary Dissection of the Dot/Icm System Based on Comparative Genomics of 58 Legionella Species

Gómez-Valero

Chiner‐Oms

Comas

et al. 2019

Genome Biology and Evolution

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The Dot/Icm type IVB secretion system of Legionella pneumophila is essential for its pathogenesis by delivering >300 effector proteins into the host cell. However, their precise secretion mechanism and which components interact with the host cell is only partly understood. Here, we undertook evolutionary analyses of the Dot/Icm system of 58 Legionella species to identify those components that interact with the host and/or the substrates. We show that high recombination rates are acting on DotA, DotG, and IcmX, supporting exposure of these proteins to the host. Specific amino acids under positive selection on the periplasmic region of DotF, and the cytoplasmic domain of DotM, support a role of these regions in substrate binding. Diversifying selection acting on the signal peptide of DotC suggests its interaction with the host after cleavage. Positive selection acts on IcmR, IcmQ, and DotL revealing that these components are probably participating in effector recognition and/or translocation. Furthermore, our results predict the participation in host/effector interaction of DotV and IcmF. In contrast, DotB, DotO, most of the core subcomplex elements, and the chaperones IcmS-W show a high degree of conservation and not signs of recombination or positive selection suggesting that these proteins are under strong structural constraints and have an important role in maintaining the architecture/function of the system. Thus, our analyses of recombination and positive selection acting on the Dot/Icm secretion system predicted specific Dot/Icm components and regions implicated in host interaction and/or substrate recognition and translocation, which will guide further functional analyses.

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Section: Resultsmentioning

confidence: 99%

“…2013). An alignment of IcmR from different bacteria was used to define the essential residues of this IcmR NAD + domain (Farelli et al. 2013).…”

Section: Resultsmentioning

confidence: 99%

Evolutionary Dissection of the Dot/Icm System Based on Comparative Genomics of 58 Legionella Species

Gómez-Valero

Chiner‐Oms

Comas

et al. 2019

Genome Biology and Evolution

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“…Recently, the structure of full-length IcmQ in complex with IcmR was solved, revealing that the C-terminal domain of IcmQ contains an NAD + binding module. The presence of this module suggests that the IcmR–IcmQ complex binds to membranes, where the NAD(+)-bound form of the complex might promote stabilizing interactions with, or modification of, a protein in the Dot/Icm machine (Farelli et al 2013). …”

Section: Function Structure and Diversification Of T4ass And T4bsssmentioning

confidence: 99%

Biological Diversity and Evolution of Type IV Secretion Systems

Christie¹,

Gómez-Valero

Buchrieser

2017

Current Topics in Microbiology and Immunology

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The bacterial type IV secretion systems (T4SSs) are a highly functionally and structurally diverse superfamily of secretion systems found in many species of gram-negative and -positive bacteria. Collectively, the T4SSs can translocate DNA and monomeric and multimeric protein substrates to a variety of bacterial and eukaryotic cell types. Detailed phylogenomics analyses have established that the T4SSs evolved from ancient conjugation machines whose original functions were to disseminate mobile DNA elements within and between bacterial species. How members of the T4SS superfamily evolved to recognize and translocate specific substrate repertoires to prokaryotic or eukaryotic target cells is a fascinating question from evolutionary, biological, and structural perspectives. In this chapter, we will summarize recent findings that have shaped our current view of the biological diversity of the T4SSs. We focus mainly on two subtypes, designated as the types IVA (T4ASS) and IVB (T4BSS) systems that respectively are represented by the paradigmatic Agrobacterium tumefaciens VirB/VirD4 and Legionella pneumophila Dot/Icm T4SSs. We present current information about the composition and architectures of these representative systems. We also describe how these and a few related T4ASS and T4BSS members evolved as specialized nanomachines through acquisition of novel domains or subunits, a process that ultimately generated extensive genetic and structural mosaicism among this secretion superfamily. Finally, we present new phylogenomics information establishing that the T4BSSs are much more broadly distributed than initially envisioned.

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“…These toxins, generally found in Gram‐positive pathogenic organisms, are known to misregulate host processes such as actin cytoskeleton and microtubule dynamics by post‐translationally modifying key host small GTPases . The toxin‐specific activity has not been reported for Legionella, however, the ADPRTs have been detected and a structure of a homolog, IcmQ, critical for T4BSS functionality, has been described . These reports confirm the presence of ADPRT domains in Legionella, however their specific function, especially of those associated with HD domains, remains to be investigated.…”

Section: Resultsmentioning

confidence: 86%

Crystal structure of the Legionella pneumophila lem10 effector reveals a new member of the HD protein superfamily

et al. 2015

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Legionella pneumophila , the intracellular pathogen that can cause severe pneumonia known as Legionnaire’s disease, translocates close to 300 effectors inside the host cell using Dot/Icm type IVB secretion system. The structure and function for the majority of these effector proteins remains unknown. Here, we present the crystal structure of the L. pneumophila effector Lem10. The structure reveals a multidomain organization with the largest C-terminal domain showing strong structural similarity to the HD protein superfamily representatives. However, Lem10 lacks the catalytic His-Asp residue pair and does not show any in vitro phosphohydrolase enzymatic activity, typical for HD proteins. While the biological function of Lem10 remains elusive, our analysis shows that similar distinct features are shared by a significant number of HD domains found in Legionella proteins, including the SidE family of effectors known to play an important role during infection. Taken together our data point to the presence of a specific group of non-catalytic Legionella HD domains, dubbed LHDs, which are involved in pathogenesis.

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IcmQ in the Type 4b Secretion System Contains an NAD+ Binding Domain

Cited by 6 publications

References 57 publications

Evolutionary Dissection of the Dot/Icm System Based on Comparative Genomics of 58 Legionella Species

Evolutionary Dissection of the Dot/Icm System Based on Comparative Genomics of 58 Legionella Species

Biological Diversity and Evolution of Type IV Secretion Systems

Crystal structure of the Legionella pneumophila lem10 effector reveals a new member of the HD protein superfamily

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