title: Chemical cross-linking and native mass spectrometry: A fruitful combination for structural biology.
abstract: Mass spectrometry (MS) is becoming increasingly popular in the field of structural biology for analyzing protein three-dimensional-structures and for mapping protein-protein interactions. In this review, the specific contributions of chemical crosslinking and native MS are outlined to reveal the structural features of proteins and protein assemblies. Both strategies are illustrated based on the examples of the tetrameric tumor suppressor protein p53 and multisubunit vinculin-Arp2/3 hybrid complexes. We describe the distinct advantages and limitations of each technique and highlight synergistic effects when both techniques are combined. Integrating both methods is especially useful for characterizing large protein assemblies and for capturing transient interactions. We also point out the future directions we foresee for a combination of in vivo crosslinking and native MS for structural investigation of intact protein assemblies.
authors.affiliation: Department of Pharmaceutical Chemistry & Bioanalytics, Institute of Pharmacy, Martin-Luther University Halle-Wittenberg, D-06120, Halle, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sinz
authors.affiliation: Department of Pharmaceutical Chemistry & Bioanalytics, Institute of Pharmacy, Martin-Luther University Halle-Wittenberg, D-06120, Halle, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Arlt
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Dror
authors.initials: D
authors.lastname: Chorev
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Sharon
mesh_terms: D000818:Animals; D003432:Cross-Linking Reagents / Q000737:chemistry*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D008958:Models, Molecular; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism
chemical_list: D003432:Cross-Linking Reagents; D011506:Proteins; D016159:Tumor Suppressor Protein p53
keywords: chemical cross-linking; native mass spectrometry; protein 3D structure; protein-protein interactions