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-Structure paper
タイトル | Cryo-EM of Mitotic Checkpoint Complex-Bound APC/C Reveals Reciprocal and Conformational Regulation of Ubiquitin Ligation. |
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ジャーナル・号・ページ | Mol Cell, Vol. 63, Issue 4, Page 593-607, Year 2016 |
掲載日 | 2016年8月18日 |
著者 | Masaya Yamaguchi / Ryan VanderLinden / Florian Weissmann / Renping Qiao / Prakash Dube / Nicholas G Brown / David Haselbach / Wei Zhang / Sachdev S Sidhu / Jan-Michael Peters / Holger Stark / Brenda A Schulman / |
PubMed 要旨 | The mitotic checkpoint complex (MCC) coordinates proper chromosome biorientation on the spindle with ubiquitination activities of CDC20-activated anaphase-promoting complex/cyclosome (APC/C(CDC20)). ...The mitotic checkpoint complex (MCC) coordinates proper chromosome biorientation on the spindle with ubiquitination activities of CDC20-activated anaphase-promoting complex/cyclosome (APC/C(CDC20)). APC/C(CDC20) and two E2s, UBE2C and UBE2S, catalyze ubiquitination through distinct architectures for linking ubiquitin (UB) to substrates and elongating polyUB chains, respectively. MCC, which contains a second molecule of CDC20, blocks APC/C(CDC20)-UBE2C-dependent ubiquitination of Securin and Cyclins, while differentially determining or inhibiting CDC20 ubiquitination to regulate spindle surveillance, checkpoint activation, and checkpoint termination. Here electron microscopy reveals conformational variation of APC/C(CDC20)-MCC underlying this multifaceted regulation. MCC binds APC/C-bound CDC20 to inhibit substrate access. However, rotation about the CDC20-MCC assembly and conformational variability of APC/C modulate UBE2C-catalyzed ubiquitination of MCC's CDC20 molecule. Access of UBE2C is limiting for subsequent polyubiquitination by UBE2S. We propose that conformational dynamics of APC/C(CDC20)-MCC modulate E2 activation and determine distinctive ubiquitination activities as part of a response mechanism ensuring accurate sister chromatid segregation. |
リンク | Mol Cell / PubMed:27522463 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 4.8 - 18.0 Å |
構造データ | EMDB-4021: Human Anaphase-Promoting Complex/Cyclosome (APC/C) APC15 deletion mutant with Mitotic Checkpoint Complex (MCC) in a closed conformation. EMDB-4022: EMDB-4023: EMDB-4024: EMDB-4025: Human Anaphase-promoting complex/Cyclosome (APC/C) APC15 deletion mutant bound to the E2 UBE2C (aka UBCH10) poised for ubiquitin ligation to substrate. EMDB-4026: EMDB-4027: EMDB-4028: |
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キーワード | CELL CYCLE / ubiquitination / protein complex / mitosis / inhibition / conformational change |