Structure of full-length p53 tumor suppressor probed by chemical cross-linking and mass spectrometry

Proteomics
Christian ArltAndrea Sinz

Abstract

The tumor suppressor p53 presents a great challenge for 3D structural analysis due to its inherent flexibility. In this work, we gained insight into the structure of full-length wild-type human p53 in solution by chemical cross-linking/MS. This approach allowed us obtaining structural information of free wild-type p53 in solution without making use of the ultrastable quadruple p53 variant. The cross-links within one p53 monomer are in good agreement with the small-angle X-ray scattering based model of full-length p53. Our cross-linking data between different p53 molecules in the tetramer however indicate a large degree of flexibility in the C-terminal regulatory domain of full-length p53 in the absence of DNA. The cross-links suggest that the C-terminal regulatory domains are much closer to each other, resulting in a more compact arrangement of the p53 tetramer than perceived by the small-angle X-ray scattering model.

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Oct 27, 2015·Journal of Molecular Biology·Carla SchmidtCarol V Robinson
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Sep 7, 2019·Analytical Chemistry·Emeline HanozinEdwin De Pauw
Feb 8, 2020·Journal of the American Society for Mass Spectrometry·Christian H IhlingAndrea Sinz

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