Results and Discussion Structures of Human Cdc20 by Itself or in Complex with BubR1 KEN1. We propose that this low-cooperativity, multisite substrate recognition mechanism expands the substrate spectrum of APC/C, allowing it to attenuate the cellular concentrations of myriad substrates with one or more functional degrons. A single functional APC/C degron within a substrate supports APC/C Cdh1-dependent ubiquitination. Our results indicate that the multiple APC/C degrons of securin do not engage APC/C in a highly cooperative manner. D-box peptides inhibit APC/C-mediated ubiquitination of KEN-box substrates, suggesting competition between the two motifs. This lack of strong cooperativity between the two degrons also applies to APC/C Cdh1, but the KEN and D boxes have comparable contributions in this case. The KEN box is largely dispensable for securin ubiquitination by APC/C Cdc20.

Surprisingly, despite binding to distinct sites on Cdc20, the KEN and D boxes of securin do not apparently interact with APC/C in a highly cooperative manner. Structure-based mutagenesis then defined a second conserved surface on the side of the ОІ propeller as a D-box-contacting site. To better understand how APC/C recognizes its substrates, we determined the crystal structures of human Cdc20 alone or bound to the KEN1 box of BubR1, revealing a preexisting KEN-box-binding site at the top of the WD40 ОІ propeller. We propose that low-cooperativity, multisite target recognition enables APC/C to robustly ubiquitinate diverse substrates and helps to drive cell cycle oscillations. Our results indicate the lack of strong positive cooperativity between the two degrons of securin. Furthermore, D-box peptides diminish the ubiquitination of KEN-box substrates by APC/C Cdh1, suggesting possible competition between the two motifs.

Although both motifs contribute to securin ubiquitination by APC/C Cdh1, securin mutants lacking either motif are efficiently ubiquitinated. The D box of securin, but not its KEN box, is critical for securin ubiquitination by APC/C Cdc20. We identify a second conserved surface at the side of the Cdc20 ОІ propeller as a D-box-binding site. Cdc20 has a disordered N-terminal region and a C-terminal WD40 ОІ propeller with a preformed KEN-box-binding site at its top face. We report the crystal structures of human Cdc20 alone or bound to a BubR1 KEN box.

How APC/C recognizes substrates is not understood. Checkpoint inhibition of APC/C Cdc20 requires the binding of a BubR1 KEN box to Cdc20. APC/C Cdc20 is the target of the spindle checkpoint. The mitotic APC/C activator, the cell division cycle 20 (Cdc20) protein, directly interacts with APC/C degronsвЂ“вЂ“the destruction (D) and KEN boxes. However, customer support is still available through Microsoft SupportВ and Microsoft products are available through our partners in the region.The anaphase-promoting complex/cyclosome (APC/C) promotes anaphase onset and mitotic exit through ubiquitinating securin and cyclin B1. Lebanon Microsoft Store for consumers closed on October 28, 2021.

Microsoft has suspended all new sales of products and services in Russia. Microsoft Store Sales and Customer Support

Dbox support