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MTMDAT-HADDOCK: high-throughput, data-driven protein complex structure modeling
Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology . Linköping University, The Institute of Technology.
Bijvoet Center for Biomolecular Research, Science Faculty, Utrecht University, 3584 CH Utrecht, The Netherlands.
Department of Informatics, Gabriele-von-B¨ulow Gymnasium, DE-13509 Berlin, Germany.
Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology . Linköping University, The Institute of Technology.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: MTMDAT is a recently developed program facilitating the analysis of mass spectrometry data of proteins and biomolecular complexes (Hennig et al, 2008), which were structurally probed by limited proteolysis. This can provide information about stable fragments of multidomain proteins, yields tertiary and quaternary structure data, and residue-wise origins of stability changes can be determined.

Results: A new feature allows for the direct identification of residues that are involved in complex formation bycomparing the mass spectra of bound and unbound proteins after proteolysis. If 3D structures of the unboundcomponents are available, this data can be used to restrain data-driven docking to calculate the structure ofthe complex. Here, we provide a new implementation of MTMDAT, with a pipeline to the data-driven dockingprogram HADDOCK (Dominguez et al., 2003; De Vries et al., 2007), streamlining the entire procedure. This,together with usability improvements in MTMDAT, enables direct high-throughput modelling of protein complexesfrom mass spectrometry data.

Conclusions: MTMDAT can be downloaded from¯sunnerhagens¯group/mtmdat/ (windows- or unix-based, with or without HADDOCK pipeline) together withthe manual and example files. The program is free for academic/non-commercial purposes.

National Category
Natural Sciences
URN: urn:nbn:se:liu:diva-53169OAI: diva2:287359
Available from: 2010-01-18 Created: 2010-01-18 Last updated: 2010-01-18
In thesis
1. Structure-function studies on TRIM21/Ro52, a protein involved in autoimmune diseases
Open this publication in new window or tab >>Structure-function studies on TRIM21/Ro52, a protein involved in autoimmune diseases
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Several members of the tripartite motif (TRIM) protein family are involvedin antiviral activity and immunity and have been linked to severaldiseases. TRIM21, the main object of this thesis, is involved in Sjögrensyndrome (SS) and systemic lupus erythematosus (SLE), where patientsoften have autoantibodies against different epitopes on TRIM21. Duringthe course of this study a role of TRIM21 in regulation of proinflammatorycytokines and autoimmunity emerged. The aim of this thesis is to providea better understanding of the structure-function relationship of TRIM21.A conformational epitope in the coiled-coil domain of TRIM21 has beencharacterized, whose autoantibodies cause congenital heart block. A widerange of biophysical methods were employed to establish a model of theprotein domain arrangement of TRIM21, and functional implications werederived. By sequence comparisons, TRIM proteins were classified into threesubgroups, sharing a conserved amphipathic helix in the region, linkingthe conserved N-terminal Zn2+-binding domains RING and B-box, calledthe RING-B-box linker (RBL). A structural dependence of this region on theRING has been observed and a model of the RING-RBL was derived frombioinformatics and proteolysis data. Anti-RING-RBL antibodies inhibit theE3 ligase activity of TRIM21 in ubiquitination. Interferon regulatory factors(IRFs), the substrate for TRIM21-dependent ubiquitination could thereforeretain their high cellular levels after stress-induced inflammation, increasingthe susceptibility to SS and SLE. According to NMR data, the antibodiesbind to the Zn2+-binding loop regions of the RING, which usually bind tothe E2 conjugating enzyme. Antibodies against the C-terminus of the RBLregion do not inhibit the E3 ligase activity.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2009. 89 p.
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1272
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
urn:nbn:se:liu:diva-52744 (URN)978-91-7393-538-8 (ISBN)
Public defence
2009-10-30, Planck, Fysikhuset, Campus Valla, Linköpings universitet, Linköping, 13:15 (English)
Available from: 2010-01-18 Created: 2010-01-12 Last updated: 2010-01-18Bibliographically approved

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