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

Interaction	Experimental Evidence Code	Dataset	Throughput	Score	Curated By	Notes
HIST1H3A RPL3	Proximity Label-MS Proximity Label-MS An interaction is inferred when a bait-enzyme fusion protein selectively modifies a vicinal protein with a diffusible reactive product, followed by affinity capture of the modified protein and identification by mass spectrometric methods.	Liu X (2018)	High	-	BioGRID	-

Curated By

BioGRID

Interaction Summary

HIST1H3A

Gene Ontology Biological Process

Gene Ontology Molecular Function

protein binding [IPI]

Gene Ontology Cellular Component

RPL3