Cross-Linking-MS (XL-MS)

An interaction is detected between two proteins using chemically reactive or photo-activatable cross-linking reagents that covalently link amino acids in close proximity, followed by mass spectrometry analysis to identify the linked peptides (reviewed in PMID 37406423, 37104977). Experiments may be carried with live cells or cell lysates in which all proteins are expressed at endogenous levels (e.g. PMID 34349018, 35235311) or with recombinant proteins (e.g., PMID 28537071).

Publication

Cysteine-enabled cleavability to advance cross-linking mass spectrometry for global analysis of endogenous protein-protein interactions.

Jiao F, Braitbard M, Yu C, Shor B, Wulff BE, Schneidman-Duhovny D, Huang L

Cross-linking mass spectrometry (XL-MS) is a powerful technology for probing protein-protein interactions (PPIs) and elucidating architectures of protein complexes at the systems level. While successful, the proteome coverage remains limited. To expand the scope of global PPI profiling, we introduce an innovative cysteine-based cleavable XL-MS platform using non-cleavable heterobifunctional lysine-cysteine (K-C) cross-linkers. The oxidation-induced transformation of cysteine cleavability enables unambiguous ... [more]

Nat Commun Dec. 12, 2025; 16(1);11093 [Pubmed: 41387687]

Throughput

  • High Throughput

Related interactions

InteractionExperimental Evidence CodeDatasetThroughputScoreCurated ByNotes
PFN1 CFL1
Co-fractionation
Co-fractionation

Interaction inferred from the presence of two or more protein subunits in a partially purified protein preparation. If co-fractionation is demonstrated between 3 or more proteins, then add them as a complex.

High0.0905BioGRID
1259928

Curated By

  • BioGRID