Fig. 3: The N-terminal domain of Orc6 docks onto the ORC·Cdc6 ring through interactions with Orc1 and Cdc6.
From: A mechanism of origin licensing control through autoinhibition of S. cerevisiae ORC·DNA·Cdc6
a Unsharpened cryo-EM map and schematic of ScORC·DNA·Cdc6 with a docked N-terminal cyclin box domain (CBN) of Orc6. The flexible linker between N- and C-terminal CB folds is indicated by a dashed line. b Scheme of ScOrc6’s domain architecture. CBN and CBC share structural similarity with transcription factor TFIIB, which is predicated on cyclin box folds. c and d Orc6-CBN directly docks onto the Cdc6 WH domain and the lid subdomain of the Orc1 AAA+ fold. Interacting domains are rendered as colored cartoon in (c). A zoomed view of the binding site is shown in (d) with interacting side chain residues rendered as sticks and hydrogen bonds and salt bridges displayed by dashed lines. e Crosslinks between Orc1, Cdc6, and Orc6 identified by mass spectrometry. Cyan lines highlight crosslinks involving Orc6-CBN or the proximal linker region immediately following this domain. The number of crosslink-spectra matches (CSM) is listed for each crosslink. See Supplementary Fig. 8c for a summary of observed crosslinks between all subunits in ScORC·DNA·Cdc6. CB – cyclin box domain, CTD – C-terminal domain, WH – winged-helix domain, BAH – bromo-adjacent homology domain.
