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Structure of full‐length p53 tumor suppressor probed by chemical cross‐linking and mass spectrometry
Author(s) -
Arlt Christian,
Ihling Christian H.,
Sinz Andrea
Publication year - 2015
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201400549
Subject(s) - tetramer , flexibility (engineering) , mass spectrometry , scattering , molecule , small angle x ray scattering , suppressor , chemistry , crystallography , biophysics , physics , biology , optics , biochemistry , chromatography , gene , statistics , mathematics , organic chemistry , enzyme
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.