Electron microscopy studies on the quaternary structure of p53 reveal different binding modes for p53 tetramers in complex with DNA
作者： R. Melero , S. Rajagopalan , M. Lazaro , A. C. Joerger , T. Brandt
关键词: Plasma protein binding 、 Protein structure 、 Förster resonance energy transfer 、 Mutation 、 HMG-box 、 Biology 、 Crystallography 、 DNA sequencing 、 DNA 、 Protein quaternary structure 、 Biophysics
摘要: The multidomain homotetrameric tumor suppressor p53 has two modes of binding dsDNA that are thought to be responsible for scanning and recognizing specific response elements (REs). C termini bind nonspecifically dsDNA. four DNA-binding domains (DBDs) REs have symmetric 10 base-pair sequences. bound a 20-bp RE the DBDs enveloping DNA, which is in center molecule surrounded by linker sequences tetramerization domain (Tet). We investigated electron microscopy structures DNA consisting with either 12 or 20 bp nonspecific extensions on end. found variety give clues recognition mechanisms. 44- 60-bp gave rise three classes structures, respectively. One was similar known structure, but other were loosely arranged incompatible recognition. Some complexes had density consistent C termini extending from Tet adjacent DBDs. Single-molecule fluorescence resonance energy transfer experiments detected approach towards addition DNA. structural data sliding along via its hopping off during searches REs. loose posttranslational modifications account affinity point mechanism enhancement specificity effector proteins.
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