The beginning of a beautiful friendship: cross-linking/mass spectrometry and modelling of proteins and multi-protein complexes

By Juri Rappsilber. 2010

427 citations recorded by the source corpus.

After more than a decade of method development, cross-linking in combination with mass spectrometry and bioinformatics is finally coming of age. This technology now provides improved opportunities for modelling by mapping structural details of functional complexes in solution. The structure of proteins or protein complexes is ascertained by identifying amino acid pairs that are positioned in close proximity to each other. The validity of this technique has recently been benchmarked for large multi-protein complexes, by comparing cross-link data with that from a crystal structure of RNA polymerase II. Here, the specific nature of this cross-linking data will be discussed to assess the technical challenges and opportunities for model building. We believe that once cross-linking/mass spectrometry data has been incorporated into modelling algorithms it will quickly become an indispensable companion of protein and protein complex modelling and a corner-stone of integrated structural biology.

Subfields: Materials Chemistry, Molecular Biology, Spectroscopy

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Citations in the corpus

Critical Assessment of Methods of Protein Structure Prediction (CASP) – Progress and New directions in Round XI (2016, background): “…alternative requiring smaller samples (nano to micromolar), simpler protocols, in many cases shorter time to obtain the structure, and lower costs.42 ,43 Residue–residue distance restraints, obtained from analysis of cross linked peptides, allow the generation of protein–protein interaction maps…”
Principles of assembly reveal a periodic table of protein complexes (2015, methodology): “This could be further integrated into hybrid methods combining different experimental measurements (30), such as electrospray (31) or cross-linking (32) mass spectrometry.”
Blind testing of cross‐linking/mass spectrometry hybrid methods in CASP11 (2016, result): “Since we would like to capture the impact of CLMS data, we only compared the best predictions from groups that submitted predictions to both experiments [19 groups, Fig.”
Serum Albumin Domain Structures in Human Blood Serum by Mass Spectrometry and Computational Biology (2015, background): “The distance constraints obtained are sparse but complement other structural data in integrated structural biology well (10).”
High Sensitivity Crosslink Detection Coupled With Integrative Structure Modeling in the Mass Spec Studio * (2016, methodology): “We identified 64 crosslinked peptides (41 unique ones, after removal of multiple charge states) using the probabilistic criteria presented above ( i.e. a transformed E-score of (cid:6) 13).”