Structure of full-length p53 tumor suppressor probed by chemical cross-linking and mass spectrometry.
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.
Department of Pharmaceutical Chemistry and Bioanalytics, Institute of Pharmacy, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany.
Christian
C
Arlt
Department of Pharmaceutical Chemistry and Bioanalytics, Institute of Pharmacy, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany.
Christian H
CH
Ihling
Department of Pharmaceutical Chemistry and Bioanalytics, Institute of Pharmacy, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany.
Andrea
A
Sinz
D000595:Amino Acid Sequence; D003432:Cross-Linking Reagents; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009587:Nitrogen Isotopes / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry*
D003432:Cross-Linking Reagents; D064267:Intrinsically Disordered Proteins; D009587:Nitrogen Isotopes; D016159:Tumor Suppressor Protein p53
3D structure; Chemical cross-linking; Intrinsically disordered proteins; MS; Technology; p53