The role of auxiliary domains in modulating CHD4 activity suggests mechanistic commonality between enzyme families

Yichen Zhong, Hakimeh Moghaddas Sani, Bishnu P. Paudel, Jason K. K. Low, Ana P. G. Silva, Stefan Mueller, Chandrika Deshpande, Santosh Panjikar, Xavier J. Reid, Max J. Bedward, Antoine M. Oijen () and Joel P. Mackay ()
Additional contact information
Yichen Zhong: University of Sydney
Hakimeh Moghaddas Sani: University of Sydney
Bishnu P. Paudel: University of Wollongong
Jason K. K. Low: University of Sydney
Ana P. G. Silva: University of Sydney
Stefan Mueller: University of Wollongong
Chandrika Deshpande: University of Sydney
Santosh Panjikar: Australian Synchrotron
Xavier J. Reid: University of Sydney
Max J. Bedward: University of Sydney
Antoine M. Oijen: University of Wollongong
Joel P. Mackay: University of Sydney

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract CHD4 is an essential, widely conserved ATP-dependent translocase that is also a broad tumour dependency. In common with other SF2-family chromatin remodelling enzymes, it alters chromatin accessibility by repositioning histone octamers. Besides the helicase and adjacent tandem chromodomains and PHD domains, CHD4 features 1000 residues of N- and C-terminal sequence with unknown structure and function. We demonstrate that these regions regulate CHD4 activity through different mechanisms. An N-terminal intrinsically disordered region (IDR) promotes remodelling integrity in a manner that depends on the composition but not sequence of the IDR. The C-terminal region harbours an auto-inhibitory region that contacts the helicase domain. Auto-inhibition is relieved by a previously unrecognized C-terminal SANT-SLIDE domain split by ~150 residues of disordered sequence, most likely by binding of this domain to substrate DNA. Our data shed light on CHD4 regulation and reveal strong mechanistic commonality between CHD family members, as well as with ISWI-family remodellers.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-35002-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35002-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-35002-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().