Biomolecular NMR Assignments

, Volume 13, Issue 1, pp 85–89 | Cite as

Backbone and side-chain chemical shift assignments of full-length, apo, human Pin1, a phosphoprotein regulator with interdomain allostery

  • Alexandra Born
  • Parker J. Nichols
  • Morkos A. Henen
  • Celestine N. Chi
  • Dean Strotz
  • Peter Bayer
  • Shin-Ichi Tate
  • Jeffrey W. Peng
  • Beat VögeliEmail author


Pin1 is a human peptidyl-prolyl cistrans isomerase important for the regulation of phosphoproteins that are implicated in many diseases including cancer and Alzheimer’s. Further biophysical study of Pin1 will elucidate the importance of the two-domain system to regulate its own activity. Here, we report near-complete backbone and side-chain 1H, 13C and 15N NMR chemical shift assignments of full-length, apo Pin1 for the purpose of studying interdomain allostery and dynamics.


Pin1 Prolyl isomerase NMR Chemical shift assignments Allostery 



We would like to thank Dr. David Jones at University of Colorado for helping set up initial experiments. This work was supported by a start-up package from the University of Colorado at Denver to B.V.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.


  1. Apic G, Gough J, Teichmann SA (2001) Domain combinations in archaeal, eubacterial and eukaryotic proteomes. J Mol Biol 310:311–325. CrossRefGoogle Scholar
  2. Bao L, Kimzey A, Sauter G et al (2004) Prevalent overexpression of prolyl isomerase Pin1 in human cancers. Am J Pathol 164:1727–1737. CrossRefGoogle Scholar
  3. Bayer E, Goettsch S, Mueller JW et al (2003) Structural analysis of the mitotic regulator hPin1 in solution: insights into domain architecture and substrate binding. J Biol Chem 278:26183–26193. CrossRefGoogle Scholar
  4. Blair LJ, Baker JD, Sabbagh JJ, Dickey CA (2015) The emerging role of peptidyl-prolyl isomerase chaperones in tau oligomerization, amyloid processing, and Alzheimer’s disease. J Neurochem 133:1–13. CrossRefGoogle Scholar
  5. Born A, Henen M, Nichols P et al (2018) Efficient stereospecific Hβ2/3 NMR assignment strategy for mid-size proteins. Magnetochemistry 4:25. CrossRefGoogle Scholar
  6. Butterfield DA, Abdul HM, Opii W et al (2006) REVIEW: Pin1 in Alzheimer’s disease. J Neurochem 98:1697–1706. CrossRefGoogle Scholar
  7. Delaglio F, Grzesiek S, Vuister GW et al (1995) NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J Biomol NMR 6:277–293CrossRefGoogle Scholar
  8. Ekman D, Björklund ÅK, Frey-Skött J, Elofsson A (2005) Multi-domain proteins in the three kingdoms of life: orphan domains and other unassigned regions. J Mol Biol 348:231–243. CrossRefGoogle Scholar
  9. Jacobs DM, Saxena K, Grimme S et al (2002) 1H, 13C and 15N backbone resonance assignment of the peptidyl-prolyl cis-trans isomerase Pin1. J Biomol NMR 23:163–164CrossRefGoogle Scholar
  10. Jacobs DM, Saxena K, Vogtherr M et al (2003) Peptide binding induces large scale changes in inter-domain mobility in human Pin1. J Biol Chem 278:26174–26182. CrossRefGoogle Scholar
  11. Kowalski JA, Liu K, Kelly JW (2002) NMR solution structure of the isolated Apo Pin1 WW domain: comparison to the X-ray crystal structures of Pin1. Biopolymers 63:111–121. CrossRefGoogle Scholar
  12. Liou Y-C, Zhou XZ, Lu KP (2011) Prolyl isomerase Pin1 as a molecular switch to determine the fate of phosphoproteins. Trends Biochem Sci 36:501–514. CrossRefGoogle Scholar
  13. Lu KP, Hanes SD, Hunter T (1996) A human peptidyl–prolyl isomerase essential for regulation of mitosis. Nature 380:544–547. ADSCrossRefGoogle Scholar
  14. Matena A, Sinnen C, Van Den Boom J et al (2013) Transient domain interactions enhance the affinity of the mitotic regulator pin1 toward phosphorylated peptide ligands. Structure 21:1769–1777. CrossRefGoogle Scholar
  15. Namanja AT, Peng T, Zintsmaster JS et al (2007) Substrate recognition reduces side-chain flexibility for conserved hydrophobic residues in human Pin1. Structure 15:313–327. CrossRefGoogle Scholar
  16. Namanja AT, Wang XJ, Xu B et al (2011) Stereospecific gating of functional motions in Pin1. Proc Natl Acad Sci 108:12289–12294. ADSCrossRefGoogle Scholar
  17. Peng JW (2015) Investigating dynamic interdomain allostery in Pin1. Biophys Rev 7:239–249. ADSCrossRefGoogle Scholar
  18. Ranganathan R, Lu KP, Hunter T, Noel JP (1997) Structural and functional analysis of the mitotic rotamase Pin1 suggest substrate recognition is phosphorylation dependent. Cell 89:875–886CrossRefGoogle Scholar
  19. Rustighi A, Zannini A, Tiberi L et al (2014) Prolyl-isomerase Pin1 controls normal and cancer stem cells of the breast. EMBO Mol Med 6:99–119. CrossRefGoogle Scholar
  20. Shen M, Stukenberg PT, Kirschner MW, Lu KP (1998) The essential mitotic peptidyl-prolyl isomerase Pin1 binds and regulates mitosis-specific phosphoproteins. Genes Dev 12:706–720CrossRefGoogle Scholar
  21. Strotz D (2016) eNOE method development and applications to protein allostery. PhD Thesis Dissertation No. 23867, ETH ZurichGoogle Scholar
  22. Ubersax JA, Ferrell JE Jr (2007) Mechanisms of specificity in protein phosphorylation. Nat Rev Mol Cell Biol 8:530–541. CrossRefGoogle Scholar
  23. Vranken WF, Boucher W, Stevens TJ et al (2005) The CCPN data model for NMR spectroscopy: development of a software pipeline. Proteins Struct Funct Bioinform 59:687–696. CrossRefGoogle Scholar
  24. Wilson KA, Bouchard JJ, Peng JW (2013) Interdomain interactions support interdomain communication in human pin1. Biochemistry 52:6968–6981. CrossRefGoogle Scholar
  25. Xu N, Tochio N, Wang J et al (2014) The C113D mutation in human Pin1 causes allosteric structural changes in the phosphate binding pocket of the ppiase domain through the tug of war in the dual-histidine motif. Biochemistry 53:5568–5578. CrossRefGoogle Scholar
  26. Zhang M, Case DA, Peng JW (2018) Propagated perturbations from a peripheral mutation show interactions supporting WW domain thermostability. Struct Des. Google Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular GeneticsUniversity of Colorado Anschutz Medical CampusAuroraUSA
  2. 2.Faculty of PharmacyMansoura UniversityMansouraEgypt
  3. 3.Department of Medical Biochemistry and MicrobiologyUppsala UniversityUppsalaSweden
  4. 4.Laboratory of Physical ChemistryETH Zürich, ETH-HönggerbergZurichSwitzerland
  5. 5.Strukturelle und Medizinische BiochemieUniversität Duisburg-EssenEssenGermany
  6. 6.Department of Mathematical and Life SciencesHiroshima UniversityHiroshimaJapan
  7. 7.Department of Chemistry and Biochemistry & Department of PhysicsUniversity of Notre DameNotre DameUSA
  8. 8.Department of Biochemistry and Molecular GeneticsUniversity of Colorado DenverAuroraUSA

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