Abstract：
:PTPA, an essential and specific activator of protein phosphatase 2A (PP2A), functions as a peptidyl prolyl isomerase (PPIase). We present here the crystal structures of human PTPA and of the two yeast orthologs (Ypa1 and Ypa2), revealing an all alpha-helical protein fold that is radically different from other PPIases. The protein is organized into two domains separated by a groove lined by highly conserved residues. To understand the molecular mechanism of PTPA activity, Ypa1 was cocrystallized with a proline-containing PPIase peptide substrate. In the complex, the peptide binds at the interface of a peptide-induced dimer interface. Conserved residues of the interdomain groove contribute to the peptide binding site and dimer interface. Structure-guided mutational studies showed that in vivo PTPA activity is influenced by mutations on the surface of the peptide binding pocket, the same mutations that also influenced the in vitro activation of PP2Ai and PPIase activity.
journal_name
Mol Celljournal_title
Molecular cellauthors
Leulliot N,Vicentini G,Jordens J,Quevillon-Cheruel S,Schiltz M,Barford D,van Tilbeurgh H,Goris Jdoi
10.1016/j.molcel.2006.07.008subject
Has Abstractpub_date
2006-08-04 00:00:00pages
413-24issue
3eissn
1097-2765issn
1097-4164pii
S1097-2765(06)00488-6journal_volume
23pub_type
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