6VRO

The structure of the PP2A B56 subunit AIM1 complex

Summary for 6VRO

• Entry DOI: 10.2210/pdb6vro/pdb
• Descriptor: Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform, Beta/gamma crystallin domain-containing protein 1 (3 entities in total)
• Functional Keywords: ser/thr phosphatase, complex, hydrolase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 44710.79

Authors

Wang, X.,Page, R.,Peti, W. (deposition date: 2020-02-08, release date: 2020-03-25, Last modification date: 2023-10-11)

Primary citation

Wang, X.,Garvanska, D.H.,Nasa, I.,Ueki, Y.,Zhang, G.,Kettenbach, A.N.,Peti, W.,Nilsson, J.,Page, R.
A dynamic charge-charge interaction modulates PP2A:B56 substrate recruitment.
Elife, 9:-, 2020

PubMed Abstract: The recruitment of substrates by the ser/thr protein phosphatase 2A (PP2A) is poorly understood, limiting our understanding of PP2A-regulated signaling. Recently, the first PP2A:B56 consensus binding motif, LxxIxE, was identified. However, most validated LxxIxE motifs bind PP2A:B56 with micromolar affinities, suggesting that additional motifs exist to enhance PP2A:B56 binding. Here, we report the requirement of a positively charged motif in a subset of PP2A:B56 interactors, including KIF4A, to facilitate B56 binding via dynamic, electrostatic interactions. Using molecular and cellular experiments, we show that a conserved, negatively charged groove on B56 mediates dynamic binding. We also discovered that this positively charged motif, in addition to facilitating KIF4A dephosphorylation, is essential for condensin I binding, a function distinct and exclusive from PP2A-B56 binding. Together, these results reveal how dynamic, charge-charge interactions fine-tune the interactions mediated by specific motifs, providing a new framework for understanding how PP2A regulation drives cellular signaling.

PubMed: 32195664
DOI: 10.7554/eLife.55966

Experimental method

X-RAY DIFFRACTION (2.45 Å)