title: Intrinsic disorder in proteins: a challenge for (un)structural biology met by ion mobility-mass spectrometry.
abstract: The link between structure and function of a given protein is a principal tenet of biology. The established approach to understand the function of a protein is to 'solve' its structure and subsequently investigate interactions between the protein and its binding partners. However, structure determination via crystallography or NMR is challenging for proteins where localized regions or even their entire structure fail to fold into a three-dimensional form. These so called IDPs (intrinsically disordered proteins) or intrinsically disordered regions constitute up to 40% of all expressed proteins, and a much higher percentage in proteins involved in the proliferation of cancer. For these proteins, there is a need to develop new methods for structural characterization which exploit their biophysical properties. IM (ion mobility)-MS is uniquely able to examine both absolute conformation(s), populations of conformation and also conformational change, and is therefore highly applicable to the study of IDPs. The present article details the technique of IM-MS and illustrates its use in assessing the relative disorder of the wild-type p53 DNA-core-binding domain of cellular tumour antigen p53. The IM data were acquired on a Waters Synapt HDMS instrument following nESI (nanoelectrospray ionization) from 'native' and low-pH solution conditions.
authors.affiliation: EaStChem School of Chemistry, University of Edinburgh, Joseph Black Building, West Mains Road, Edinburgh EH9 3JJ, U.K.
authors.forename: Ewa
authors.initials: E
authors.lastname: Jurneczko
authors.forename: Faye
authors.initials: F
authors.lastname: Cruickshank
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Porrini
authors.forename: Penka
authors.initials: P
authors.lastname: Nikolova
authors.forename: Iain D G
authors.initials: ID
authors.lastname: Campuzano
authors.forename: Michael
authors.initials: M
authors.lastname: Morris
authors.forename: Perdita E
authors.initials: PE
authors.lastname: Barran
mesh_terms: D006863:Hydrogen-Ion Concentration; D013058:Mass Spectrometry; D011487:Protein Conformation; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53