1k3q › Citations

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 314 563-75 (2001)
Related entries: 1g3g, 1j4o, 1j4p, 1j4q, 1k3j, 1k3n

Cited: 26 times
EuropePMC logo PMID: 11846567

Abstract

Rad53, a yeast checkpoint protein involved in regulating the repair of DNA damage, contains two forkhead-associated domains, FHA1 and FHA2. Previous combinatorial library screening has shown that FHA1 strongly selects peptides containing a pTXXD motif. Subsequent location of this motif within the sequence of Rad9, the target protein, coupled with spectroscopic analysis has led to identification of a tight binding sequence that is likely the binding site of FHA1: (188)SLEV(pT)EADATFVQ(200). We present solution structures of FHA1 in complex with this pT-peptide and with another Rad9-derived pT-peptide that has ca 30-fold lower affinity, (148)KKMTFQ(pT)PTDPLE(160). Both complexes showed intermolecular NOEs predominantly between three peptide residues (pT, +1, and +2 residues) and five FHA1 residues (S82, R83, S85, T106, and N107). Furthermore, the following interactions were implicated on the basis of chemical shift perturbations and structural analysis: the phosphate group of the pT residue with the side-chain amide group of N86 and the guanidino group of R70, and the carboxylate group of Asp (at the +3 position) with the guanidino group of R83. The generated structures revealed a similar binding mode adopted by these two peptides, suggesting that pT and the +3 residue Asp are the major contributors to binding affinity and specificity, while +1 and +2 residues could provide additional fine-tuning. It was also shown that FHA1 does not bind to the corresponding pS-peptides or a related pY-peptide. We suggest that differentiation between pT and pS-peptides by FHA1 can be attributed to hydrophobic interactions between the methyl group of the pT residue and the aliphatic protons of R83, S85, and T106 from FHA1.

Articles - 1k3q mentioned but not cited (3)

  1. Damped-dynamics flexible fitting. Kovacs JA, Yeager M, Abagyan R. Biophys J 95 3192-3207 (2008)
  2. Mechanism of PhosphoThreonine/Serine Recognition and Specificity for Modular Domains from All-atom Molecular Dynamics. Huang YM, Chang CE. BMC Biophys 4 12 (2011)
  3. Achieving peptide binding specificity and promiscuity by loops: case of the forkhead-associated domain. Huang YM, Chang CE. PLoS One 9 e98291 (2014)


Reviews citing this publication (3)

  1. The Chk2 protein kinase. Ahn J, Urist M, Prives C. DNA Repair (Amst) 3 1039-1047 (2004)
  2. Mechanistic insights into phosphoprotein-binding FHA domains. Liang X, Van Doren SR. Acc Chem Res 41 991-999 (2008)
  3. Protein-protein interactions: from global to local analyses. Kelly W, Stumpf M. Curr Opin Biotechnol 19 396-403 (2008)

Articles citing this publication (20)

  1. 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)
  2. 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)
  3. Mechanisms of checkpoint kinase Rad53 inactivation after a double-strand break in Saccharomyces cerevisiae. Guillemain G, Ma E, Mauger S, Miron S, Thai R, Guérois R, Ochsenbein F, Marsolier-Kergoat MC. Mol Cell Biol 27 3378-3389 (2007)
  4. Rad53 checkpoint kinase phosphorylation site preference identified in the Swi6 protein of Saccharomyces cerevisiae. Sidorova JM, Breeden LL. Mol Cell Biol 23 3405-3416 (2003)
  5. Pellino proteins contain a cryptic FHA domain that mediates interaction with phosphorylated IRAK1. Lin CC, Huoh YS, Schmitz KR, Jensen LE, Ferguson KM. Structure 16 1806-1816 (2008)
  6. 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)
  7. 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)
  8. 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)
  9. Structure-based prediction of protein-peptide specificity in Rosetta. King CA, Bradley P. Proteins 78 3437-3449 (2010)
  10. Crystal structure of Arabidopsis thaliana Dawdle forkhead-associated domain reveals a conserved phospho-threonine recognition cleft for dicer-like 1 binding. Machida S, Yuan YA. Mol Plant 6 1290-1300 (2013)
  11. 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)
  12. 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)
  13. 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)
  14. FHA: a signal transduction domain with diverse specificity and function. Tsai MD. Structure 10 887-888 (2002)
  15. A strategy for interaction site prediction between phospho-binding modules and their partners identified from proteomic data. Aucher W, Becker E, Ma E, Miron S, Martel A, Ochsenbein F, Marsolier-Kergoat MC, Guerois R. Mol Cell Proteomics 9 2745-2759 (2010)
  16. alpha-Helical burst on the folding pathway of FHA domains from Rad53 and Ki67. Matsumura Y, Shinjo M, Mahajan A, Tsai MD, Kihara H. Biochimie 92 1031-1039 (2010)
  17. Characterization of the APLF FHA-XRCC1 phosphopeptide interaction and its structural and functional implications. Kim K, Pedersen LC, Kirby TW, DeRose EF, London RE. Nucleic Acids Res 45 12374-12387 (2017)
  18. 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)
  19. Bibliography Current awareness on yeast. Yeast 19 565-572 (2002)
  20. Bibliography Current awareness on yeast. Yeast 19 651-658 (2002)


Related citations provided by authors (1)

  1. 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 304 941-51 (2000)

Quick links