TFIIB and TFIID are polymerase II specific general transcription initiation factors. TFIID recognizes and binds to the TATA element, coordinating the formation of a functional preinitiation complex. TFIID is a multisubunit complex composed of the TATA-box binding protein (TBP) and several other tightly associated polypeptides (TAFs). TFIIB recognizes and binds to the TFIID-DNA promoter complex and facilitates the subsequent interaction with RNA polymerase II. The binding of TFIIB can be the rate-limiting step and consequently a target for transcriptional activation. TBP and TFIIB as well as their interactions are studies by X-ray crystallography, surface plasmon resonance, circular spectroscopy, analytical ultracentrifugation, and mass spectrometry. MALDI-MS was used to determined the relative resistant of TFIIB towards intermolecular crosslinking due to oxidation (i.e. disulfide bond formation). Protein-DNA cocrystals, grown from a solution containing the three components of the ternary complex, were analyzed for their composition using MALDI-MS unequivocally showed the presence of all three components and indicated equimolar levels of the two proteins in the cocrystal. A manuscript describing this work has been published in the journal NATURE.