Structural Architecture of the Nucleosome Remodeler ISWI Determined from Cross-Linking, Mass Spectrometry, SAXS, and Modeling

Harrer, Nadine; Schindler, Christina; Bruetzel, Linda K.; Forné, Ignasi; Ludwigsen, Johanna; Imhof, Axel; Zacharias, Martin; Lipfert, Jan; Mueller-Planitz, Felix

doi:10.1016/j.str.2017.12.015

Cited by 12 publications

(16 citation statements)

References 77 publications

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“…The filtered Sequest HT output files for each peptide were grouped according to the protein from which they were derived. Cross-linked peptides were analyzed on a Q Exactive HF (Thermo) mass spectrometer as described ( 37 ) and mapped with the program “Crossfinder” as described ( 38 , 39 ) using the following filter settings: number of fragment ions per spectrum > 5, number of fragment ions per peptide > 2, fractional intensity of assigned MS2 peaks > 0.05, and score > 2 00.…”

Section: Methodsmentioning

confidence: 99%

A case of convergent evolution: Several viral and bacterial pathogens hijack RSK kinases through a common linear motif

Sorgeloos

Peeters

Hayashi

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Microbes have been coevolving with their host for millions of years, exploiting host resources to their own benefit. We show that viral and bacterial pathogens convergently evolved to hijack cellular mitogen-activated protein kinase (MAPK) p90-ribosomal S6-kinases (RSKs). Theiler’s virus leader (L) protein binds RSKs and prevents their dephosphorylation, thus maintaining the kinases active. Recruitment of RSKs enables L-protein-mediated inhibition of eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2 or PKR) and stress granule formation. Strikingly, ORF45 protein of Kaposi’s sarcoma-associated herpesvirus (KSHV) and YopM protein of Yersinia use the same peptide motif as L to recruit and activate RSKs. All three proteins interact with a conserved surface-located loop of RSKs, likely acting as an allosteric regulation site. Some unrelated viruses and bacteria thus evolved to harness RSKs in a common fashion, yet to target distinct aspects of innate immunity. As documented for Varicella zoster virus ORF11, additional pathogens likely evolved to hijack RSKs, using a similar short linear motif.

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Section: Methodsmentioning

confidence: 99%

A case of convergent evolution: Several viral and bacterial pathogens hijack RSK kinases through a common linear motif

Sorgeloos

Peeters

Hayashi

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

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“…XL-MS is a very compelling technique relative to other methods for mapping interactions, because of the ability of XL-MS to generate high-accuracy models in a variety of experimental contexts, from isolated proteins to in vivo interactions. − A range of cross-linking methods exist that are relatively straightforward to implement in a higher-throughput fashion. ,− Most XL-MS studies have relied on amine-reactive chemistries involving N -hydroxysuccinimide (NHS) esters, as exemplified by disuccinimidyl suberate (DSS) and bis(sulfosuccinimidyl)suberate (BS 3 ). While these have generated abundant cross-links, NHS-ester chemistry is less than ideal given its selectivity toward lysine , and the slow accumulation of reaction products .…”

Section: Introductionmentioning

confidence: 99%

Photo-Cross-Linking Mass Spectrometry and Integrative Modeling Enables Rapid Screening of Antigen Interactions Involving Bacterial Transferrin Receptors

Ziemianowicz

Schryvers

et al. 2018

J. Proteome Res.

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Structure-based approaches to the delineation of immunogens for vaccine development have a throughput requirement that is difficult to meet in practice with conventional methods of structure determination. Here we present a strategy for rapid and accurate structure generation in support of antigen engineering programs. The approach is developed around the modeling of interactions between host transferrin (Tf) and the bacterial vaccine target transferrin binding protein B (TbpB) from Gram-negative pathogens such as Neisseria meningitidis. Using an approach based solely on cross-linking mass spectrometry (XL-MS) data, monomeric structural models, and the Integrative Modeling Platform (IMP), we demonstrate that converged representations of the Tf:TbpB interactions can be returned that accurately reflect the binding interface and the relative orientation of the monomeric units, with the capacity to scale to the analysis of interactions from any number of additional strains. We show that a key element to accurate modeling involves the application of hetero-bifunctional cross-linkers incorporating fast-acting photoactivatable diazirines coupled with conventional amine-targeting N-hydroxysuccinimide esters, and we demonstrate that conventional homo-bifunctional reagents used in cross-linking kinetically trap dynamic states in the ensemble. Therefore, the application of both classes of cross-linker provides an opportunity to empirically detect protein dynamics during integrative structural modeling.

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“…The availability of crystal structures of ISWI subunits provided a unique strategy to develop their selective antagonists. To date, the crystal structures of ISWI subunits in some species have been elucidated to different resolution [144][145][146][147]…”

Section: Iswi Complexes As Potential Targets For Cancer Therapymentioning

confidence: 99%

The emerging role of ISWI chromatin remodeling complexes in cancer

Gong

Wang

et al. 2021

J Exp Clin Cancer Res

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Disordered chromatin remodeling regulation has emerged as an essential driving factor for cancers. Imitation switch (ISWI) family are evolutionarily conserved ATP-dependent chromatin remodeling complexes, which are essential for cellular survival and function through multiple genetic and epigenetic mechanisms. Omics sequencing and a growing number of basic and clinical studies found that ISWI family members displayed widespread gene expression and genetic status abnormalities in human cancer. Their aberrant expression is closely linked to patient outcome and drug response. Functional or componential alteration in ISWI-containing complexes is critical for tumor initiation and development. Furthermore, ISWI-non-coding RNA regulatory networks and some non-coding RNAs derived from exons of ISWI member genes play important roles in tumor progression. Therefore, unveiling the transcriptional regulation mechanism underlying ISWI family sparked a booming interest in finding ISWI-based therapies in cancer. This review aims at describing the current state-of-the-art in the role of ISWI subunits and complexes in tumorigenesis, tumor progression, immunity and drug response, and presenting deep insight into the physiological and pathological implications of the ISWI transcription machinery in cancers.

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Structural Architecture of the Nucleosome Remodeler ISWI Determined from Cross-Linking, Mass Spectrometry, SAXS, and Modeling

Cited by 12 publications

References 77 publications

A case of convergent evolution: Several viral and bacterial pathogens hijack RSK kinases through a common linear motif

A case of convergent evolution: Several viral and bacterial pathogens hijack RSK kinases through a common linear motif

Photo-Cross-Linking Mass Spectrometry and Integrative Modeling Enables Rapid Screening of Antigen Interactions Involving Bacterial Transferrin Receptors

The emerging role of ISWI chromatin remodeling complexes in cancer

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