5KHR

Model of human Anaphase-promoting complex/Cyclosome complex (APC15 deletion mutant) in complex with the E2 UBE2C/UBCH10 poised for ubiquitin ligation to substrate (APC/C-CDC20-substrate-UBE2C)

Summary for 5KHR

• Entry DOI: 10.2210/pdb5khr/pdb
• Related: 5KHU
• EMDB information: 4021 4025
• Descriptor: Anaphase-promoting complex subunit 1, Anaphase-promoting complex subunit 13, Anaphase-promoting complex subunit 2, ... (16 entities in total)
• Functional Keywords: ubiquitination, cell cycle, protein complex, mitosis
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus : Q9BS18 P30260 Q8NHZ8; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome : Q12834 Q13042; Cytoplasm : Q9NYG5 Q96DE5
• Total number of polymer chains: 21
• Total formula weight: 1231156.22

Authors

VanderLinden, R.,Yamaguchi, M.,Dube, P.,Haselbach, D.,Stark, H.,Schulman, B.A. (deposition date: 2016-06-15, release date: 2016-08-24, Last modification date: 2024-03-06)

Primary citation

Yamaguchi, M.,VanderLinden, R.,Weissmann, F.,Qiao, R.,Dube, P.,Brown, N.G.,Haselbach, D.,Zhang, W.,Sidhu, S.S.,Peters, J.M.,Stark, H.,Schulman, B.A.
Cryo-EM of Mitotic Checkpoint Complex-Bound APC/C Reveals Reciprocal and Conformational Regulation of Ubiquitin Ligation.
Mol.Cell, 63:593-607, 2016

PubMed Abstract: 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.

PubMed: 27522463
DOI: 10.1016/j.molcel.2016.07.003

Experimental method

ELECTRON MICROSCOPY (6.1 Å)