6ASZ

Chromodomain HP1 with Y24F mutation bound to histone H3 peptide containing trimethyl lysine

Replaces:  5KOG

Summary for 6ASZ

• Entry DOI: 10.2210/pdb6asz/pdb
• Descriptor: Heterochromatin protein 1, trimethyl lysine histone H3 tail peptide (3 entities in total)
• Functional Keywords: histone reader, transcription
• Biological source: Drosophila melanogaster (Fruit fly); More
• Total number of polymer chains: 2
• Total formula weight: 9304.33

Authors

Brustad, E.M.,Baril, S.A.,Waters, M.L. (deposition date: 2017-08-27, release date: 2017-12-06, Last modification date: 2023-10-04)

Primary citation

Baril, S.A.,Koenig, A.L.,Krone, M.W.,Albanese, K.I.,He, C.Q.,Lee, G.Y.,Houk, K.N.,Waters, M.L.,Brustad, E.M.
Investigation of Trimethyllysine Binding by the HP1 Chromodomain via Unnatural Amino Acid Mutagenesis.
J. Am. Chem. Soc., 139:17253-17256, 2017

PubMed Abstract: Trimethyllysine (Kme3) reader proteins are targets for inhibition due to their role in mediating gene expression. Although all such reader proteins bind Kme3 in an aromatic cage, the driving force for binding may differ; some readers exhibit evidence for cation-π interactions whereas others do not. We report a general unnatural amino acid mutagenesis approach to quantify the contribution of individual tyrosines to cation binding using the HP1 chromodomain as a model system. We demonstrate that two tyrosines (Y24 and Y48) bind to a Kme3-histone tail peptide via cation-π interactions, but linear free energy trends suggest they do not contribute equally to binding. X-ray structures and computational analysis suggest that the distance and degree of contact between Tyr residues and Kme3 plays an important role in tuning cation-π-mediated Kme3 recognition. Although cation-π interactions have been studied in a number of proteins, this work is the first to utilize direct binding assays, X-ray crystallography, and modeling, to pinpoint factors that influence the magnitude of the individual cation-π interactions.

PubMed: 29111699
DOI: 10.1021/jacs.7b09223

Experimental method

X-RAY DIFFRACTION (1.518 Å)