6CZO

The KNL1-PP1 Holoenzyme

Summary for 6CZO

• Entry DOI: 10.2210/pdb6czo/pdb
• Descriptor: Serine/threonine-protein phosphatase PP1-alpha catalytic subunit, CASC5 protein, MANGANESE (II) ION, ... (5 entities in total)
• Functional Keywords: phosphatase, regulator, slim, kinetochore, hydrolase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 82631.89

Authors

Bajaj, R.,Peti, W.,Page, R. (deposition date: 2018-04-09, release date: 2019-01-23, Last modification date: 2023-10-04)

Primary citation

Bajaj, R.,Bollen, M.,Peti, W.,Page, R.
KNL1 Binding to PP1 and Microtubules Is Mutually Exclusive.
Structure, 26:1327-1336.e4, 2018

PubMed Abstract: The kinetochore scaffold 1 (KNL1) protein coordinates the spindle assembly checkpoint (SAC), a signaling pathway that delays chromosome segregation until all sister chromatids are properly attached to spindle microtubules. Recently, microtubules and protein phosphatase 1 (PP1), which both bind the N-terminal domain of KNL1, have emerged as regulators of the SAC; however, how these proteins interact to contribute to SAC signaling is unknown. Here, we use X-ray crystallography, nuclear magnetic resonance spectroscopy, and biochemical assays to show how KNL1 binds both PP1 and microtubules. Unexpectedly, we discovered that PP1 and microtubules bind KNL1 via overlapping binding sites. Further, we showed that Aurora B kinase phosphorylation results in distinct patterns of KNL1 complex disruption. Finally, combining this data with co-sedimentation assays unequivocally demonstrated that microtubules and PP1 binding to KNL1 is mutually exclusive, with preferential formation of the KNL1:PP1 holoenzyme in the presence of PP1.

PubMed: 30100357
DOI: 10.1016/j.str.2018.06.013

Experimental method

X-RAY DIFFRACTION (2.95 Å)