To cleave or not to cleave: a systemic evaluation of DSS versus DSSO for cross-linking mass spectrometry analysis (opens in new tab)

Cross-linking mass spectrometry is a powerful method for structural analysis, but choosing between cleavable and non-cleavable cross-linkers remains challenging. We rigorously compared non-cleavable DSS with cleavable DSSO and found that DSS consistently yields more cross-link identifications from isolated protein complexes to bacterial lysates. The advantage of DSS diminishes as sample complexity increases. At the highest complexity tested—human cell lysate—the trend reverses, with DSSO outp...