Research output: Contribution to journal › Article › peer-review
Histone H4 tails in nucleosomes: a fuzzy interaction with DNA. / Рабдано, Севастьян Олегович; Shannon, M.; Измайлов, Сергей Александрович; Gonzalez Salguero, N.; Zandian, M.; Purusottam, Rudra N.; Poirier, M.; Jaroniec, Christopher; Скрынников, Николай Русланович.
In: Angewandte Chemie - International Edition, Vol. 60, No. 12, 15.03.2021, p. 6480-6487.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Histone H4 tails in nucleosomes: a fuzzy interaction with DNA
AU - Рабдано, Севастьян Олегович
AU - Shannon, M.
AU - Измайлов, Сергей Александрович
AU - Gonzalez Salguero, N.
AU - Zandian, M.
AU - Purusottam, Rudra N.
AU - Poirier, M.
AU - Jaroniec, Christopher
AU - Скрынников, Николай Русланович
N1 - Publisher Copyright: © 2021 Wiley-VCH GmbH
PY - 2021/3/15
Y1 - 2021/3/15
N2 - The interaction of positively charged N-terminal histone tails with nucleosomal DNA plays an important role in chromatin assembly and regulation, modulating their susceptibility to post-translational modifications and recognition by chromatin-binding proteins. Here, we report residue-specific 15N NMR relaxation rates for histone H4 tails in reconstituted nucleosomes. These data indicate that H4 tails are strongly dynamically disordered, albeit with reduced conformational flexibility compared to a free peptide with the same sequence. Remarkably, the NMR observables were successfully reproduced in a 2-μs MD trajectory of the nucleosome. This is an important step toward resolving an apparent inconsistency where prior simulations were generally at odds with experimental evidence on conformational dynamics of histone tails. Our findings indicate that histone H4 tails engage in a fuzzy interaction with nucleosomal DNA, underpinned by a variable pattern of short-lived salt bridges and hydrogen bonds, which persists at low ionic strength (0–100 mM NaCl).
AB - The interaction of positively charged N-terminal histone tails with nucleosomal DNA plays an important role in chromatin assembly and regulation, modulating their susceptibility to post-translational modifications and recognition by chromatin-binding proteins. Here, we report residue-specific 15N NMR relaxation rates for histone H4 tails in reconstituted nucleosomes. These data indicate that H4 tails are strongly dynamically disordered, albeit with reduced conformational flexibility compared to a free peptide with the same sequence. Remarkably, the NMR observables were successfully reproduced in a 2-μs MD trajectory of the nucleosome. This is an important step toward resolving an apparent inconsistency where prior simulations were generally at odds with experimental evidence on conformational dynamics of histone tails. Our findings indicate that histone H4 tails engage in a fuzzy interaction with nucleosomal DNA, underpinned by a variable pattern of short-lived salt bridges and hydrogen bonds, which persists at low ionic strength (0–100 mM NaCl).
KW - NMR spectroscopy
KW - fuzzy protein–DNA interactions
KW - histone tails
KW - molecular dynamics
KW - nucleosome
KW - DNA/chemistry
KW - Histones/chemistry
KW - Nucleosomes/chemistry
KW - WATER MODEL
KW - SIDE-CHAINS
KW - CORE PARTICLES
KW - INTRINSICALLY DISORDERED PROTEINS
KW - N-TERMINAL PEPTIDES
KW - DNA interactions
KW - H4-K16 ACETYLATION
KW - STRUCTURAL DISORDER
KW - DYNAMICS
KW - fuzzy protein–
KW - FORCE-FIELD
KW - SALT BRIDGES
UR - http://www.scopus.com/inward/record.url?scp=85100839099&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/0a1b7985-3365-32c0-a987-c3b897f4291c/
U2 - 10.1002/anie.202012046
DO - 10.1002/anie.202012046
M3 - Article
C2 - 33522067
VL - 60
SP - 6480
EP - 6487
JO - ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
JF - ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
SN - 1433-7851
IS - 12
ER -
ID: 73378489