Cytochrome C and lysozyme were purchased from Sigma. Cross-linking of these proteins followed the same procedure as described previously.30 (link)Cross-linked peptides were analyzed by LC MSn utilizing an LTQ-Orbitrap XL MS (Thermo Fisher, San Jose, CA) coupled on-line with an Easy-nLC 1000 (Thermo Fisher, San Jose, CA) as previously described.3 (link),7 (link) Each MSn experiment consists of one MS scan in FT mode (350–1400 m/z, resolution of 60,000 at m/z 400) followed by two data-dependent MS2 scans in FT mode (resolution of 7500) with normalized collision energy at 20% on the top two MS peaks with charges at 3+ or up, and three MS3 scans in the LTQ with normalized collision energy at 35% on the top three peaks from each MS2.