title: Modelling the structure of latexin-carboxypeptidase A complex based on chemical cross-linking and molecular docking.
abstract: We have determined the three-dimensional structure of the protein complex between latexin and carboxypeptidase A using a combination of chemical cross-linking, mass spectrometry and molecular docking. The locations of three intermolecular cross-links were identified using mass spectrometry and these constraints were used in combination with a speed-optimised docking algorithm allowing us to evaluate more than 3 x 10(11) possible conformations. While cross-links represent only limited structural constraints, the combination of only three experimental cross-links with very basic molecular docking was sufficient to determine the complex structure. The crystal structure of the complex between latexin and carboxypeptidase A4 determined recently allowed us to assess the success of this structure determination approach. Our structure was shown to be within 4 A r.m.s. deviation of Calpha atoms of the crystal structure. The study demonstrates that cross-linking in combination with mass spectrometry can lead to efficient and accurate structural modelling of protein complexes.
authors.affiliation: School of Molecular and Microbial Sciences, Institute for Molecular Bioscience, Cooperative Research Centre for Chronic Inflammatory Diseases, Department of Mathematics, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Mouradov
authors.forename: Ari
authors.initials: A
authors.lastname: Craven
authors.forename: Jade K
authors.initials: JK
authors.lastname: Forwood
authors.forename: Jack U
authors.initials: JU
authors.lastname: Flanagan
authors.forename: Raquel
authors.initials: R
authors.lastname: García-Castellanos
authors.forename: F Xavier
authors.initials: FX
authors.lastname: Gomis-Rüth
authors.forename: David A
authors.initials: DA
authors.lastname: Hume
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Martin
authors.forename: Bostjan
authors.initials: B
authors.lastname: Kobe
authors.forename: Thomas
authors.initials: T
authors.lastname: Huber
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000941:Antigens / Q000737:chemistry* / Q000378:metabolism; D043422:Carboxypeptidases A / Q000737:chemistry* / Q000378:metabolism; D003198:Computer Simulation; D003432:Cross-Linking Reagents / Q000737:chemistry*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D000941:Antigens; D003432:Cross-Linking Reagents; C086812:Lxn protein, rat; D043422:Carboxypeptidases A