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Structural probing of a protein phosphatase 2A network by chemical cross-linking and mass spectrometry.

Citation Herzog, Franz; Kahraman, Abdullah; Boehringer, Daniel; Mak, Raymond; Bracher, Andreas; Walzthoeni, Thomas; Leitner, Alexander; Beck, Martin; Hartl, Franz-Ulrich; Ban, Nenad; Malmstrom, Lars; Aebersold, Ruedi; Structural probing of a protein phosphatase 2A network by chemical cross-linking and mass spectrometry. Science (2012), 337: 1348-52.
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.
Synopsis Protein complexes were crosslinked and messured using mass spectrometry. The identified crosslinks specify a maximum distance between different parts of the proteins in the complex and this information can be used to build computer models of the complexes.
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