Book of Abstracts: Albany 2009

category image Albany 2009
Conversation 16
June 16-20 2009
© Adenine Press (2008)

Architecture and Regulation of the CHD1 Chromatin Remodeler

Chromatin remodelers use a core ATPase motor in conjunction with auxiliary domains to assemble, move, and evict nucleosomes from DNA. In order to better understand how remodeler domains communicate, we solved the crystal structure of the ATPase module from the yeast CHD1 remodeler coupled to the N-terminal double chromodomains. Both lobes of the ATPase module, which must close together to engage their double-stranded DNA substrate and hydrolyze ATP, interact with the double chromodomains and appear to be stabilized in an opened, catalytically inactive conformation. In addition to being unable to hydrolyze ATP, the opened conformation prevents the two ATPase lobes from simultaneously interacting with duplex DNA. Interestingly, one of the contact surfaces between the chromodomains and ATPase module corresponds to the predicted DNA-binding surface of the second ATPase lobe. The structure suggests that the chromodomains directly compete with DNA for binding to the ATPase motor, and thus inhibit ATP hydrolysis. Site-directed mutagenesis and deletion analysis indicates that the chromodomain/ATPase interface is required for nucleosome-specific activation of the ATPase motor, and disruption of this interface allows the ATPase motor to be stimulated by naked DNA. We discuss implications for ATPase regulation during chromatin remodeling.

G. Hauk1
J. Mcknight1,2
I. M. Nodelman1
G. D. Bowman1,2

1TC Jenkins Department of Biophysics
2Department of Biology
Johns Hopkins University
Baltimore MD 21218

Email: gdbowman@jhu.edu