Journal ArticleDOI
Structural Probing of a Protein Phosphatase 2A Network by Chemical Cross-Linking and Mass Spectrometry
Franz Herzog,Abdullah Kahraman,Daniel Boehringer,Raymond H. Mak,Andreas Bracher,Thomas Walzthoeni,Alexander Leitner,Martin Beck,Franz-Ulrich Hartl,Nenad Ban,Lars Malmström,Ruedi Aebersold +11 more
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TLDR
This study establishes XL-MS as an integral part of hybrid structural biology approaches for the analysis of endogenous protein complexes by gaining distance restraints on a modular interaction network of protein complexes affinity-purified from human cells by applying an adaptedXL-MS protocol.Abstract:
The identification of proximate amino acids by chemical cross-linking and mass spectrometry (XL-MS) facilitates the structural analysis of homogeneous protein complexes. We gained distance restraints on a modular interaction network of protein complexes affinity-purified from human cells by applying an adapted XL-MS protocol. Systematic analysis of human protein phosphatase 2A (PP2A) complexes identified 176 interprotein and 570 intraprotein cross-links that link specific trimeric PP2A complexes to a multitude of adaptor proteins that control their cellular functions. Spatial restraints guided molecular modeling of the binding interface between immunoglobulin binding protein 1 (IGBP1) and PP2A and revealed the topology of TCP1 ring complex (TRiC) chaperonin interacting with the PP2A regulatory subunit 2ABG. This study establishes XL-MS as an integral part of hybrid structural biology approaches for the analysis of endogenous protein complexes.read more
Citations
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Mass-spectrometric exploration of proteome structure and function
TL;DR: Powerful mass-spectrometry-based technologies now provide unprecedented insights into the composition, structure, function and control of the proteome, shedding light on complex biological processes and phenotypes.
Journal ArticleDOI
Structure and dynamics of molecular networks: A novel paradigm of drug discovery: A comprehensive review
Peter Csermely,Tamas Korcsmaros,Tamas Korcsmaros,Huba Kiss,Gábor London,Ruth Nussinov,Ruth Nussinov +6 more
TL;DR: It is shown how network techniques can help in the identification of single-target, edgetic, multi-target and allo-network drug target candidates and an optimized protocol of network-aided drug development is suggested, and a list of systems-level hallmarks of drug quality is provided.
Journal ArticleDOI
Next-generation proteomics: towards an integrative view of proteome dynamics
TL;DR: MS-based proteomics is starting to mature and to deliver through a combination of developments in instrumentation, sample preparation and computational analysis, and to highlight recent applications.
Journal ArticleDOI
Proteome-wide profiling of protein assemblies by cross-linking mass spectrometry
TL;DR: An integrated workflow that robustly identifies cross-links from endogenous protein complexes in human cellular lysates is described, based on the application of mass spectrometry (MS)-cleavable cross-linkers, sequential collision-induced dissociation (CID)–tandem MS (MS/MS) and electron-transfer Dissociation (ETD)-MS/ MS acquisitions, and a dedicated search engine, XlinkX.
Journal ArticleDOI
Crosslinking and Mass Spectrometry: An Integrated Technology to Understand the Structure and Function of Molecular Machines.
TL;DR: An overview of recent advances in XL-MS, the current state of the field, and a cursory outlook on future challenges is provided.
References
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Journal ArticleDOI
The Protein Data Bank
Helen M. Berman,John D. Westbrook,Zukang Feng,Gary L. Gilliland,Talapady N. Bhat,Helge Weissig,Ilya N. Shindyalov,Philip E. Bourne +7 more
TL;DR: The goals of the PDB are described, the systems in place for data deposition and access, how to obtain further information and plans for the future development of the resource are described.
Journal ArticleDOI
Comparative Protein Modelling by Satisfaction of Spatial Restraints
Andrej Sali,Tom L. Blundell +1 more
TL;DR: A comparative protein modelling method designed to find the most probable structure for a sequence given its alignment with related structures, which is automated and illustrated by the modelling of trypsin from two other serine proteinases.
Journal ArticleDOI
EMBOSS: The European Molecular Biology Open Software Suite
TL;DR: The European Molecular Biology Open Software Suite is a mature package of software tools developed for the molecular biology community that includes a comprehensive set of applications for molecular sequence analysis and other tasks and integrates popular third-party software packages under a consistent interface.
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UniProt: the Universal Protein knowledgebase
Rolf Apweiler,Amos Marc Bairoch,Cathy H. Wu,Winona C. Barker,Brigitte Boeckmann,Serenella Ferro,Elisabeth Gasteiger,Hongzhan Huang,Rodrigo Lopez,Michele Magrane,Maria Jesus Martin,Darren A. Natale,Claire O'Donovan,Nicole Redaschi,Lai-Su L. Yeh +14 more
TL;DR: The Swiss-Prot, TrEMBL and PIR protein database activities have united to form the Universal Protein Knowledgebase (UniProt), which is to provide a comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase, with extensive cross-references and query interfaces.
Journal ArticleDOI
Protein secondary structure prediction based on position-specific scoring matrices
TL;DR: A two-stage neural network has been used to predict protein secondary structure based on the position specific scoring matrices generated by PSI-BLAST and achieved an average Q3 score of between 76.5% to 78.3% depending on the precise definition of observed secondary structure used, which is the highest published score for any method to date.