Design of a protein kinase-inducible domain

Journal of the American Chemical Society
Shalini Balakrishnan, Neal J Zondlo

Abstract

Protein phosphorylation is a critical regulatory strategy. New tools are necessary which may be used to interrogate and are responsive to the activities of protein kinases and phosphatases. We have used protein design to develop a protein motif, termed a protein kinase-inducible domain, whose structure is dependent on its phosphorylation state. Based on an EF hand calcium-binding loop, the key design element is the replacement of a structurally critical Glu residue, which binds metal in a bidentate manner, with a serine residue, which is expected to bind metal tightly when phosphorylated but poorly when not phosphorylated. The design comprises an EF hand consensus sequence, a tryptophan at residue 7 to sensitize lanthanide luminescence, and the recognition sequence of a serine/threonine kinase. Designed peptides, which contain minimal substrate recognition motifs of the protein kinases PKA, PKC, or the MAP kinase Erk, form complexes with Tb3+ when phosphorylated, showing strong Tb3+ luminescence emission at 544 nm, but show weak luminescence when not phosphorylated. The change in fluorescence on phosphorylation is comparable to or greater than that observed in described kinase sensors. Site-specific lanthanide binding was confi...Continue Reading

References

Apr 28, 1981·Biochemistry·A EberhardN J Oppenheimer
Feb 1, 1997·Nature Structural Biology·L SzilákC Vinson
Jun 1, 1997·Protein Science : a Publication of the Protein Society·L SzilákC Vinson
Feb 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·M SiedleckaA Bierzynski
Dec 26, 2001·Chemical Reviews·A J Bridges
May 4, 2002·Annual Review of Biophysics and Biomolecular Structure·Paul R Selvin
May 9, 2002·Journal of the American Chemical Society·Renato BarbieriAntonio Rosato
Dec 10, 2002·Science·G ManningS Sudarsanam
Apr 3, 2003·Chembiochem : a European Journal of Chemical Biology·Katherine J FranzBarbara Imperiali
May 29, 2003·Journal of the American Chemical Society·Roger T KovacicSonya J Franklin
Oct 30, 2003·Journal of the American Chemical Society·Jens WöhnertHarald Schwalbe
Nov 5, 2003·Journal of Molecular Biology·Rachel S Signarvic, William F DeGrado

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Citations

Feb 19, 2013·Analytical Chemistry·Andrew M Lipchik, Laurie L Parker
Sep 1, 2009·Chemical Reviews·Kathryn L Haas, Katherine J Franz
Apr 7, 2010·Journal of the American Chemical Society·Susan Carr ZondloNeal J Zondlo
Jun 12, 2010·Journal of the American Chemical Society·Alexander J Riemen, Marcey L Waters
Sep 12, 2009·Journal of the American Chemical Society·Alexander J Riemen, Marcey L Waters
Jun 27, 2007·Dalton Transactions : an International Journal of Inorganic Chemistry·Yumiko KataokaHiroshi Tsukube
Mar 24, 2012·The Analyst·Sanela MartićHeinz-Bernhard Kraatz
Apr 8, 2014·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Adam BuczkowskiBartlomiej Palecz
Nov 4, 2006·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Lucy L Liu, Katherine J Franz
Feb 20, 2008·Current Opinion in Chemical Biology·Benjamin E Turk
Oct 31, 2015·Analytica Chimica Acta·Jon R BeckCliff I Stains
Jun 13, 2006·Current Opinion in Structural Biology·Xavier I Ambroggio, Brian Kuhlman
Sep 22, 2015·Analytica Chimica Acta·Maia I KellyCliff I Stains
Jan 29, 2011·The Biochemical Journal·Liliana Santamaria-Kisiel, Gary S Shaw
Nov 20, 2012·Structure·Colin A SmithTanja Kortemme
Nov 20, 2014·Chemical Communications : Chem Comm·Wei Cui, Laurie L Parker
May 24, 2018·Chemical Communications : Chem Comm·Sarah H Hewitt, Stephen J Butler
Feb 14, 2015·Chemistry : a European Journal·Nan WangHeinz-Bernhard Kraatz
Dec 25, 2008·Chembiochem : a European Journal of Chemical Biology·Keith D Green, Mary Kay H Pflum
May 21, 2010·Organic & Biomolecular Chemistry·Malgorzata BroncelBeate Koksch
Jul 14, 2010·Chembiochem : a European Journal of Chemical Biology·Christopher W am EndeNeal J Zondlo
Apr 4, 2019·Organic & Biomolecular Chemistry·Feng GaoNeal J Zondlo
Oct 7, 2011·Chemical Society Reviews·Juan A González-Vera
Aug 18, 2012·Chemical Communications : Chem Comm·Elena PazosM Eugenio Vázquez
Nov 4, 2015·Proteomes·Juan A González-Vera, May C Morris
Apr 3, 2010·Organic Letters·Fengtian Xue, Christopher T Seto
Feb 18, 2015·Journal of the American Chemical Society·Andrew M LipchikLaurie L Parker
Jul 24, 2020·ACS Synthetic Biology·Daniel L WinterDominic J Glover
Apr 3, 2007·Journal of the American Chemical Society·Lisa A CapriottiJoel P Schneider
Nov 17, 2006·The Journal of Physical Chemistry. B·Rodrigo M PetoralKajsa Uvdal

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