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II. Structure and specificity of the interaction between the FHA2 domain of Rad53 and phosphotyrosyl peptides.

Wang P, Byeon IJ, Liao H, Beebe KD, Yongkiettrakul S, Pei D, Tsai MD
J Mol Biol 302 927-40 (2000)
Cited: 33 times
EuropePMC logo PMID: 10993733

Abstract

The forkhead-associated (FHA) domain is a protein module found in many proteins involved in cell signaling in response to DNA damage. It has been suggested to bind to pThr sites of its target protein. Recently we have determined the first structure of an FHA domain, FHA2 from the yeast protein Rad53, and demonstrated that FHA2 binds to a pTyr-containing peptide (826)EDI(pY)YLD(832) from Rad9, with a moderate affinity (K(d) ca. 100 microM). We now report the solution structure of the complex of FHA2 bound with this pTyr peptide. The structure shows that the phosphate group of pTyr interacts directly with three arginine residues (605, 617, and 620), and that the leucine residue at the +2 position from the pTyr interacts with a hydrophobic surface on FHA2. The sequence specificity of FHA2 was determined by screening a combinatorial pTyr library. The results clearly show that FHA2 recognizes specific sequences C-terminal to pTyr with the following consensus: XX(pY)N(1)N(2)N(3), where N(1)=Leu, Met, Phe, or Ile, N(2)=Tyr, Phe, Leu, or Met, and N(3)=Phe, Leu, or Met. Two of the selected peptides, GF(pY)LYFIR and DV(pY)FYMIR, bind FHA2 with K(d) values of 1.1 and 5.0 microM, respectively. The results, along with other recent reports, demonstrate that the FHA domain is a new class of phosphoprotein-binding domain, capable of binding both pTyr and pThr sequences.

Reviews citing this publication (6)

  1. The FHA domain. Durocher D, Jackson SP. FEBS Lett 513 58-66 (2002)
  2. Phosphoserine/threonine-binding domains. Yaffe MB, Elia AE. Curr Opin Cell Biol 13 131-138 (2001)
  3. The Chk2 protein kinase. Ahn J, Urist M, Prives C. DNA Repair (Amst) 3 1039-1047 (2004)
  4. PhosphoSerine/threonine binding domains: you can't pSERious? Yaffe MB, Smerdon SJ. Structure 9 R33-8 (2001)
  5. The use of in vitro peptide-library screens in the analysis of phosphoserine/threonine-binding domain structure and function. Yaffe MB, Smerdon SJ. Annu Rev Biophys Biomol Struct 33 225-244 (2004)
  6. Overview of protein structural and functional folds. Sun PD, Foster CE, Boyington JC. Curr Protoc Protein Sci Chapter 17 Unit 17.1 (2004)

Articles citing this publication (27)

  1. MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways. Lou Z, Minter-Dykhouse K, Wu X, Chen J. Nature 421 957-961 (2003)
  2. Rad9 phosphorylation sites couple Rad53 to the Saccharomyces cerevisiae DNA damage checkpoint. Schwartz MF, Duong JK, Sun Z, Morrow JS, Pradhan D, Stern DF. Mol Cell 9 1055-1065 (2002)
  3. Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2. Li J, Williams BL, Haire LF, Goldberg M, Wilker E, Durocher D, Yaffe MB, Jackson SP, Smerdon SJ. Mol Cell 9 1045-1054 (2002)
  4. Rad53 phosphorylation site clusters are important for Rad53 regulation and signaling. Lee SJ, Schwartz MF, Duong JK, Stern DF. Mol Cell Biol 23 6300-6314 (2003)
  5. The Chfr mitotic checkpoint protein functions with Ubc13-Mms2 to form Lys63-linked polyubiquitin chains. Bothos J, Summers MK, Venere M, Scolnick DM, Halazonetis TD. Oncogene 22 7101-7107 (2003)
  6. Direct kinase-to-kinase signaling mediated by the FHA phosphoprotein recognition domain of the Dun1 DNA damage checkpoint kinase. Bashkirov VI, Bashkirova EV, Haghnazari E, Heyer WD. Mol Cell Biol 23 1441-1452 (2003)
  7. Diphosphothreonine-specific interaction between an SQ/TQ cluster and an FHA domain in the Rad53-Dun1 kinase cascade. Lee H, Yuan C, Hammet A, Mahajan A, Chen ES, Wu MR, Su MI, Heierhorst J, Tsai MD. Mol Cell 30 767-778 (2008)
  8. Sequential phosphorylation and multisite interactions characterize specific target recognition by the FHA domain of Ki67. Byeon IJ, Li H, Song H, Gronenborn AM, Tsai MD. Nat Struct Mol Biol 12 987-993 (2005)
  9. Structure of the FHA1 domain of yeast Rad53 and identification of binding sites for both FHA1 and its target protein Rad9. Liao H, Yuan C, Su MI, Yongkiettrakul S, Qin D, Li H, Byeon IJ, Pei D, Tsai MD. J Mol Biol 304 941-951 (2000)
  10. TOJ3, a target of the v-Jun transcription factor, encodes a protein with transforming activity related to human microspherule protein 1 (MCRS1). Bader AG, Schneider ML, Bister K, Hartl M. Oncogene 20 7524-7535 (2001)
  11. Phosphorylation-independent dual-site binding of the FHA domain of KIF13 mediates phosphoinositide transport via centaurin alpha1. Tong Y, Tempel W, Wang H, Yamada K, Shen L, Senisterra GA, MacKenzie F, Chishti AH, Park HW. Proc Natl Acad Sci U S A 107 20346-20351 (2010)
  12. Crystal structure of the FHA domain of the Chfr mitotic checkpoint protein and its complex with tungstate. Stavridi ES, Huyen Y, Loreto IR, Scolnick DM, Halazonetis TD, Pavletich NP, Jeffrey PD. Structure 10 891-899 (2002)
  13. Structure of the yeast Pml1 splicing factor and its integration into the RES complex. Brooks MA, Dziembowski A, Quevillon-Cheruel S, Henriot V, Faux C, van Tilbeurgh H, Séraphin B. Nucleic Acids Res 37 129-143 (2009)
  14. Structure of human Ki67 FHA domain and its binding to a phosphoprotein fragment from hNIFK reveal unique recognition sites and new views to the structural basis of FHA domain functions. Li H, Byeon IJ, Ju Y, Tsai MD. J Mol Biol 335 371-381 (2004)
  15. Solution structure of the yeast Rad53 FHA2 complexed with a phosphothreonine peptide pTXXL: comparison with the structures of FHA2-pYXL and FHA1-pTXXD complexes. Byeon IJ, Yongkiettrakul S, Tsai MD. J Mol Biol 314 577-588 (2001)
  16. Solution structures of two FHA1-phosphothreonine peptide complexes provide insight into the structural basis of the ligand specificity of FHA1 from yeast Rad53. Yuan C, Yongkiettrakul S, Byeon IJ, Zhou S, Tsai MD. J Mol Biol 314 563-575 (2001)
  17. Mh1 domain of Smad is a degraded homing endonuclease. Grishin NV. J Mol Biol 307 31-37 (2001)
  18. Rio1 promotes rDNA stability and downregulates RNA polymerase I to ensure rDNA segregation. Iacovella MG, Golfieri C, Massari LF, Busnelli S, Pagliuca C, Dal Maschio M, Infantino V, Visintin R, Mechtler K, Ferreira-Cerca S, De Wulf P. Nat Commun 6 6643 (2015)
  19. DNA replication checkpoint signaling depends on a Rad53-Dbf4 N-terminal interaction in Saccharomyces cerevisiae. Chen YC, Kenworthy J, Gabrielse C, Hänni C, Zegerman P, Weinreich M. Genetics 194 389-401 (2013)
  20. Kinesin subfamily UNC104 contains a FHA domain: boundaries and physicochemical characterization. Westerholm-Parvinen A, Vernos I, Serrano L. FEBS Lett 486 285-290 (2000)
  21. Crystal structure of the Pml1p subunit of the yeast precursor mRNA retention and splicing complex. Trowitzsch S, Weber G, Lührmann R, Wahl MC. J Mol Biol 385 531-541 (2009)
  22. Crystal structure analysis reveals a novel forkhead-associated domain of ESAT-6 secretion system C protein in Staphylococcus aureus. Tanaka Y, Kuroda M, Yasutake Y, Yao M, Tsumoto K, Watanabe N, Ohta T, Tanaka I. Proteins 69 659-664 (2007)
  23. PhosphoThr peptide binding globally rigidifies much of the FHA domain from Arabidopsis receptor kinase-associated protein phosphatase. Ding Z, Lee GI, Liang X, Gallazzi F, Arunima A, Van Doren SR. Biochemistry 44 10119-10134 (2005)
  24. Role of the N-terminal forkhead-associated domain in the cell cycle checkpoint function of the Rad53 kinase. Pike BL, Hammet A, Heierhorst J. J Biol Chem 276 14019-14026 (2001)
  25. Reverse interactomics: decoding protein-protein interactions with combinatorial peptide libraries. Pei D, Wavreille AS. Mol Biosyst 3 536-541 (2007)
  26. Directed evolution of the forkhead-associated domain to generate anti-phosphospecific reagents by phage display. Pershad K, Wypisniak K, Kay BK. J Mol Biol 424 88-103 (2012)
  27. Identification of potential binding sites for the FHA domain of human Chk2 by in vitro binding studies. Qin D, Lee H, Yuan C, Ju Y, Tsai MD. Biochem Biophys Res Commun 311 803-808 (2003)


Related citations provided by authors (1)

  1. Structure and function of a new phosphopeptide-binding domain containing the FHA2 of Rad53. Liao H, Byeon I-JL, Tsai M-D J. Mol. Biol. 294 1041-1049 (1999)

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