Cross-Linking Mass Spectrometry for Investigating Protein Conformations and Protein–Protein Interactions─A Method for All Seasons

Piersimoni, Lolita; Kastritis, Panagiotis L.; Arlt, Christian; Sinz, Andrea

doi:10.1021/acs.chemrev.1c00786

Cited by 166 publications

(129 citation statements)

References 276 publications

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“…When choosing cross-linkers, investigators need to consider several factors, including amino acids of interest and targeting distance. We do not review details of XL/MS here, since Piersimoni et al [ 123 ] recently published a comprehensive review regarding XL/MS for studying protein higher-order structures.…”

Section: Identification Of Metal Binding Site and Resulting Conformational Changesmentioning

confidence: 99%

Mass Spectrometry-Based Structural Proteomics for Metal Ion/Protein Binding Studies

Yan-chun

Gross

2022

Biomolecules

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Metal ions are critical for the biological and physiological functions of many proteins. Mass spectrometry (MS)-based structural proteomics is an ever-growing field that has been adopted to study protein and metal ion interactions. Native MS offers information on metal binding and its stoichiometry. Footprinting approaches coupled with MS, including hydrogen/deuterium exchange (HDX), “fast photochemical oxidation of proteins” (FPOP) and targeted amino-acid labeling, identify binding sites and regions undergoing conformational changes. MS-based titration methods, including “protein–ligand interactions by mass spectrometry, titration and HD exchange” (PLIMSTEX) and “ligand titration, fast photochemical oxidation of proteins and mass spectrometry” (LITPOMS), afford binding stoichiometry, binding affinity, and binding order. These MS-based structural proteomics approaches, their applications to answer questions regarding metal ion protein interactions, their limitations, and recent and potential improvements are discussed here. This review serves as a demonstration of the capabilities of these tools and as an introduction to wider applications to solve other questions.

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Section: Identification Of Metal Binding Site and Resulting Conformational Changesmentioning

confidence: 99%

Mass Spectrometry-Based Structural Proteomics for Metal Ion/Protein Binding Studies

Yan-chun

Gross

2022

Biomolecules

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“…Again, this had technical causes, since the equivalent non-cross-linked sample failed to produce cryo-EM specimens suitable for single particle analysis, likely because of aggregation and/or denaturation of the particles in the plunge-freezing process. Even though cross-linking is a common procedure to optimise cryo-EM samples (Drulyte et al, 2018; Stark, 2010), and XL-MS has been proven to be a suitable tool to inform modelling of native structures (O’Reilly and Rappsilber, 2018; Piersimoni et al, 2022; Schneider et al, 2018), we cannot exclude that the cross-linking procedure stabilised a rare or non-native conformation of the protein sample.…”

Section: Discussionmentioning

confidence: 99%

Structure and mechanism of a novel cytomegaloviral DCAF mediating interferon antagonism

Le‐Trilling

Banchenko

Paydar

et al. 2022

Preprint

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Human cytomegalovirus (CMV) is a highly relevant pathogen, and its rodent counterparts serve as common infection models. Global proteome profiling of rat CMV-infected cells uncovered a pronounced loss of the transcription factor STAT2, which is crucial for interferon signalling. Deletion mutagenesis documented that STAT2 is targeted by the viral protein E27. Cellular and in vitro analyses showed that E27 exploits host-derived Cullin4-RING ubiquitin ligases (CRL4) to induce poly-ubiquitylation and proteasomal degradation of STAT2. Cryo-electron microscopic structure determination revealed how E27 mimics molecular surface properties of cellular CRL4 substrate receptors (DDB1- and Cullin4-associated factors, DCAFs) to displace them from the CRL4 catalytic core. Moreover, structural analyses elucidated the mechanism of STAT2 recruitment and indicate that E27-binding additionally disturbs STAT2 activation by occupying the IRF9 binding interface. For the first time, these data provide structural insights into cytomegalovirus-encoded interferon antagonism and establish an atomic model for STAT2 counteraction by CRL4 misappropriation with important implications for viral immune evasion.

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“…In addition, cross-linking mass spectrometry (XL-MS) has recently emerged to study protein interactomics on the system-wide level [ 149 ]. XL-MS is a unique technology capable of capturing the dynamic biological assemblies in their native environment and uncovering their physical interaction contacts [ 150 , 151 ]. Liu et al [ 152 ] developed an in planta chemical cross-linking-based quantitative interactomics (IPQCX–MS) workflow in Arabidopsis to study protein–protein interactions.…”

Section: Conclusion and Future Perspectivementioning

confidence: 99%

Shotgun Proteomics as a Powerful Tool for the Study of the Proteomes of Plants, Their Pathogens, and Plant–Pathogen Interactions

et al. 2022

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The interaction between plants and pathogenic microorganisms is a multifaceted process mediated by both plant- and pathogen-derived molecules, including proteins, metabolites, and lipids. Large-scale proteome analysis can quantify the dynamics of proteins, biological pathways, and posttranslational modifications (PTMs) involved in the plant–pathogen interaction. Mass spectrometry (MS)-based proteomics has become the preferred method for characterizing proteins at the proteome and sub-proteome (e.g., the phosphoproteome) levels. MS-based proteomics can reveal changes in the quantitative state of a proteome and provide a foundation for understanding the mechanisms involved in plant–pathogen interactions. This review is intended as a primer for biologists that may be unfamiliar with the diverse range of methodology for MS-based shotgun proteomics, with a focus on techniques that have been used to investigate plant–pathogen interactions. We provide a summary of the essential steps required for shotgun proteomic studies of plants, pathogens and plant–pathogen interactions, including methods for protein digestion, identification, separation, and quantification. Finally, we discuss how protein PTMs may directly participate in the interaction between a pathogen and its host plant.

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Cross-Linking Mass Spectrometry for Investigating Protein Conformations and Protein–Protein Interactions─A Method for All Seasons

Cited by 166 publications

References 276 publications

Mass Spectrometry-Based Structural Proteomics for Metal Ion/Protein Binding Studies

Mass Spectrometry-Based Structural Proteomics for Metal Ion/Protein Binding Studies

Structure and mechanism of a novel cytomegaloviral DCAF mediating interferon antagonism

Shotgun Proteomics as a Powerful Tool for the Study of the Proteomes of Plants, Their Pathogens, and Plant–Pathogen Interactions

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