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• W2087516468 abstract "The H2A–H2B histone heterodimer folds via monomeric and dimeric kinetic intermediates. Within ∼ 5 ms, the H2A and H2B polypeptides associate in a nearly diffusion limited reaction to form a dimeric ensemble, denoted I2 and I2⁎, the latter being a subpopulation characterized by a higher content of nonnative structure (NNS). The I2 ensemble folds to the native heterodimer, N2, through an observable, first-order kinetic phase. To determine the regions of structure in the I2 ensemble, we characterized 26 Ala mutants of buried hydrophobic residues, spanning the three helices of the canonical histone folds of H2A and H2B and the H2B C-terminal helix. All but one targeted residue contributed significantly to the stability of I2, the transition state and N2; however, only residues in the hydrophobic core of the dimer interface perturbed the I2⁎ population. Destabilization of I2⁎ correlated with slower folding rates, implying that NNS is not a kinetic trap but rather accelerates folding. The pattern of Φ values indicated that residues forming intramolecular interactions in the peripheral helices contributed similar stability to I2 and N2, but residues involved in intermolecular interactions in the hydrophobic core are only partially folded in I2. These findings suggest a dimerize-then-rearrange model. Residues throughout the histone fold contribute to the stability of I2, but after the rapid dimerization reaction, the hydrophobic core of the dimer interface has few fully native interactions. In the transition state leading to N2, more native-like interactions are developed and nonnative interactions are rearranged." @default.
• W2087516468 created "2016-06-24" @default.
• W2087516468 creator A5076231671 @default.
• W2087516468 creator A5076969060 @default.
• W2087516468 date "2012-01-01" @default.
• W2087516468 modified "2023-10-15" @default.
• W2087516468 title "The H2A–H2B Dimeric Kinetic Intermediate Is Stabilized by Widespread Hydrophobic Burial with Few Fully Native Interactions" @default.
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• W2087516468 doi "https://doi.org/10.1016/j.jmb.2011.11.032" @default.
• W2087516468 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3259194" @default.
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• W2087516468 hasPublicationYear "2012" @default.
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