Chemical cross-linking is becoming a valuable tool for the high-order structure determination of proteins and protein complexes. Cross-linking methodology is able to provide low-resolution structures when at least something is known already about the proteins under investigation. The suitability of top-down and bottom-up methodologies is discussed and further potential applications of chemical cross- linking of proteins, as well as combinations with other techniques such as hydrogen/deuterium exchange and molecular modeling, are suggested.

Keywords: cross-linking, protein, high order structure, mass spectrometry, top-down, bottom-up, FT-ICR