RT Journal Article
SR Electronic
T1 Molecular basis of UHRF1 allosteric activation for synergistic histone modification binding by PI5P
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.08.04.455045
DO 10.1101/2021.08.04.455045
A1 Mandal, Papita
A1 Yerkesh, Zhadyra
A1 Kharchenko, Vladlena
A1 Zandarashvili, Levani
A1 Bensaddek, Dalila
A1 Jaremko, Lukasz
A1 Black, Ben E.
A1 Fischle, Wolfgang
YR 2021
UL http://biorxiv.org/content/early/2021/08/04/2021.08.04.455045.abstract
AB Chromatin marks are recognized by distinct binding modules many of which are embedded in multidomain proteins or complexes. How the different protein functionalities of complex chromatin modulators are regulated is often unclear. Using a combination of biochemical, biophysical and structural approaches we delineated the regulation of the H3unmodified and H3K9me binding activities of the multidomain UHRF1 protein. The phosphoinositide PI5P interacts with two distant flexible linker regions of UHRF1 in a mode that is dependent on the polar head group and the acyl part of the phospholipid. The associated conformational rearrangements stably position the H3unmodified and H3K9me3 histone recognition modules of UHRF1 for multivalent and synergistic binding of the H3 tail. Our work highlights a novel molecular function for PI5P outside of the context of lipid mono- or bilayers and establishes a molecular paradigm for the allosteric regulation of complex, multidomain chromatin modulators by small cellular molecules.Competing Interest StatementThe authors have declared no competing interest.