The Actin-Binding Prolyl-Isomerase Par17 Sustains Its Substrate Selectivity by Interdomain Allostery

Anna Sternberg; Jennifer Lynne Borger; Mathilda Thies; Anja Matena; Mike Blueggel; Bianca E. Kamba; Christine Beuck; Farnusch Kaschani; Markus Kaiser; Peter Bayer

doi:10.1002/prot.26807

The Actin-Binding Prolyl-Isomerase Par17 Sustains Its Substrate Selectivity by Interdomain Allostery

Anna Sternberg
, Jennifer Lynne Borger
, Mathilda Thies
, Anja Matena
, Mike Blueggel
, Bianca E. Kamba
, Christine Beuck
, Farnusch Kaschani
, Markus Kaiser
, Peter Bayer

Research output: Contribution to journal › Article › peer-review

Abstract

The human peptidyl-prolyl-cis/trans isomerases (PPIases), Parvulin 14 and Parvulin 17, accelerate the cis/trans isomerization of Xaa-Pro moieties within protein sequences. By modulating the respective binding interfaces of their target proteins, they play a crucial role in determining the fate of their substrates within the cell. Although both enzymes share the same amino acid sequence, they have different cellular functions. This difference is due to a 25 residue N-terminal extension present in Par17 but absent in Par14. Using activity assays, NMR spectroscopy, and mass spectrometry, we demonstrate that the N-terminal extension of Par17 determines substrate selectivity by an intramolecular allosteric mechanism and exhibits a target-binding motif that interacts with actin.

Original language	English
Pages (from-to)	1481-1497
Number of pages	17
Journal	Proteins: Structure, Function and Bioinformatics
Volume	93
Issue number	9
DOIs	https://doi.org/10.1002/prot.26807
State	Published - Sep 2025
Externally published	Yes

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title = "The Actin-Binding Prolyl-Isomerase Par17 Sustains Its Substrate Selectivity by Interdomain Allostery",

abstract = "The human peptidyl-prolyl-cis/trans isomerases (PPIases), Parvulin 14 and Parvulin 17, accelerate the cis/trans isomerization of Xaa-Pro moieties within protein sequences. By modulating the respective binding interfaces of their target proteins, they play a crucial role in determining the fate of their substrates within the cell. Although both enzymes share the same amino acid sequence, they have different cellular functions. This difference is due to a 25 residue N-terminal extension present in Par17 but absent in Par14. Using activity assays, NMR spectroscopy, and mass spectrometry, we demonstrate that the N-terminal extension of Par17 determines substrate selectivity by an intramolecular allosteric mechanism and exhibits a target-binding motif that interacts with actin.",

author = "Anna Sternberg and Borger, \{Jennifer Lynne\} and Mathilda Thies and Anja Matena and Mike Blueggel and Kamba, \{Bianca E.\} and Christine Beuck and Farnusch Kaschani and Markus Kaiser and Peter Bayer",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). PROTEINS: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.",

year = "2025",

month = sep,

doi = "10.1002/prot.26807",

language = "English",

volume = "93",

pages = "1481--1497",

journal = "Proteins: Structure, Function and Bioinformatics",

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T1 - The Actin-Binding Prolyl-Isomerase Par17 Sustains Its Substrate Selectivity by Interdomain Allostery

AU - Sternberg, Anna

AU - Borger, Jennifer Lynne

AU - Thies, Mathilda

AU - Matena, Anja

AU - Blueggel, Mike

AU - Kamba, Bianca E.

AU - Beuck, Christine

AU - Kaschani, Farnusch

AU - Kaiser, Markus

AU - Bayer, Peter

PY - 2025/9

Y1 - 2025/9

N2 - The human peptidyl-prolyl-cis/trans isomerases (PPIases), Parvulin 14 and Parvulin 17, accelerate the cis/trans isomerization of Xaa-Pro moieties within protein sequences. By modulating the respective binding interfaces of their target proteins, they play a crucial role in determining the fate of their substrates within the cell. Although both enzymes share the same amino acid sequence, they have different cellular functions. This difference is due to a 25 residue N-terminal extension present in Par17 but absent in Par14. Using activity assays, NMR spectroscopy, and mass spectrometry, we demonstrate that the N-terminal extension of Par17 determines substrate selectivity by an intramolecular allosteric mechanism and exhibits a target-binding motif that interacts with actin.

AB - The human peptidyl-prolyl-cis/trans isomerases (PPIases), Parvulin 14 and Parvulin 17, accelerate the cis/trans isomerization of Xaa-Pro moieties within protein sequences. By modulating the respective binding interfaces of their target proteins, they play a crucial role in determining the fate of their substrates within the cell. Although both enzymes share the same amino acid sequence, they have different cellular functions. This difference is due to a 25 residue N-terminal extension present in Par17 but absent in Par14. Using activity assays, NMR spectroscopy, and mass spectrometry, we demonstrate that the N-terminal extension of Par17 determines substrate selectivity by an intramolecular allosteric mechanism and exhibits a target-binding motif that interacts with actin.

UR - https://www.scopus.com/pages/publications/105000368695

U2 - 10.1002/prot.26807

DO - 10.1002/prot.26807

M3 - Article

C2 - 40071814

AN - SCOPUS:105000368695

SN - 0887-3585

VL - 93

SP - 1481

EP - 1497

JO - Proteins: Structure, Function and Bioinformatics

JF - Proteins: Structure, Function and Bioinformatics

IS - 9

ER -

The Actin-Binding Prolyl-Isomerase Par17 Sustains Its Substrate Selectivity by Interdomain Allostery

Abstract

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