4IYP

structure of the nPP2Ac-alpha4 complex

Summary for 4IYP

• Entry DOI: 10.2210/pdb4iyp/pdb
• Related: 4I5L 4I5N
• Descriptor: Immunoglobulin-binding protein 1, Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform (3 entities in total)
• Functional Keywords: alpha4, pp2a, latency, helix motif, signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm : P78318 P67775
• Total number of polymer chains: 2
• Total formula weight: 43823.23

Authors

Jiang, L.,Stanevich, V.,Satyshur, K.A.,Xing, Y. (deposition date: 2013-01-29, release date: 2013-04-17, Last modification date: 2024-11-06)

Primary citation

Jiang, L.,Stanevich, V.,Satyshur, K.A.,Kong, M.,Watkins, G.R.,Wadzinski, B.E.,Sengupta, R.,Xing, Y.
Structural basis of protein phosphatase 2A stable latency.
Nat Commun, 4:1699-1699, 2013

PubMed Abstract: The catalytic subunit of protein phosphatase 2A (PP2Ac) is stabilized in a latent form by α4, a regulatory protein essential for cell survival and biogenesis of all PP2A complexes. Here we report the structure of α4 bound to the N-terminal fragment of PP2Ac. This structure suggests that α4 binding to the full-length PP2Ac requires local unfolding near the active site, which perturbs the scaffold subunit binding site at the opposite surface via allosteric relay. These changes stabilize an inactive conformation of PP2Ac and convert oligomeric PP2A complexes to the α4 complex upon perturbation of the active site. The PP2Ac-α4 interface is essential for cell survival and sterically hinders a PP2A ubiquitination site, important for the stability of cellular PP2Ac. Our results show that α4 is a scavenger chaperone that binds to and stabilizes partially folded PP2Ac for stable latency, and reveal a mechanism by which α4 regulates cell survival, and biogenesis and surveillance of PP2A holoenzymes.

PubMed: 23591866
DOI: 10.1038/ncomms2663

Experimental method

X-RAY DIFFRACTION (2.797 Å)