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Independent NMR solution structures of a human XPA fragment comprising approximately 40% of the full\u2010length protein, the minimal DNA\u2010binding domain, revealed that one\u2010third of this molecule was disordered. To better characterize structural features of full\u2010length XPA, we performed time\u2010resolved trypsin proteolysis on active recombinant <jats:italic>Xenopus<\/jats:italic> XPA (xXPA). The resulting proteolytic fragments were analyzed by electrospray ionization interface coupled to a Fourier transform ion cyclotron resonance mass spectrometry and SDS\u2010PAGE. The molecular weight of the full\u2010length xXPA determined by mass spectrometry (30922.02 daltons) was consistent with that calculated from the sequence (30922.45 daltons). Moreover, the mass spectrometric data allowed the assignment of multiple xXPA fragments not resolvable by SDS\u2010PAGE. The neural network program Predictor of Natural Disordered Regions (PONDR) applied to xXPA predicted extended disordered N\u2010 and C\u2010terminal regions with an ordered internal core. This prediction agreed with our partial proteolysis results, thereby indicating that disorder in XPA shares sequence features with other well\u2010characterized intrinsically unstructured proteins. Trypsin cleavages at 30 of the possible 48 sites were detected and no cleavage was observed in an internal region (Q85\u2010I179) despite 14 possible cut sites. For the full\u2010length xXPA, there was strong agreement among PONDR, partial proteolysis data, and the NMR structure for the corresponding XPA fragment.<\/jats:p>","DOI":"10.1110\/ps.29401","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T00:00:34Z","timestamp":1027728034000},"page":"560-571","source":"Crossref","is-referenced-by-count":96,"title":["Identification of intrinsic order and disorder in the DNA repair protein XPA"],"prefix":"10.1002","volume":"10","author":[{"given":"Lilia M.","family":"Iakoucheva","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy L.","family":"Kimzey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christophe D.","family":"Masselon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James E.","family":"Bruce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ethan C.","family":"Garner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celeste J.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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