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Titolo:
Solution structures of two FHA1-phosphothreonine peptide complexes provideinsight into the structural basis of the ligand specificity of FHA1 from yeast Rad53
Autore:
Yuan, CH; Yongkiettrakul, S; Byeon, IJL; Zhou, SZ; Tsai, MD;
Indirizzi:
Ohio State Univ, Dept Chem, Columbus, OH 43210 USA Ohio State Univ Columbus OH USA 43210 , Dept Chem, Columbus, OH 43210 USA Ohio State Univ, Dept Biochem, Columbus, OH 43210 USA Ohio State Univ Columbus OH USA 43210 ept Biochem, Columbus, OH 43210 USA Ohio State Univ, Biochem Program, Columbus, OH 43210 USA Ohio State Univ Columbus OH USA 43210 hem Program, Columbus, OH 43210 USA Ohio State Univ, Campus Chem Instrument Ctr, Columbus, OH 43210 USA Ohio State Univ Columbus OH USA 43210 trument Ctr, Columbus, OH 43210 USA
Titolo Testata:
JOURNAL OF MOLECULAR BIOLOGY
fascicolo: 3, volume: 314, anno: 2001,
pagine: 563 - 575
SICI:
0022-2836(20011130)314:3<563:SSOTFP>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
SH2 DOMAIN; BINDING; NMR; RECOGNITION; SENSITIVITY; CHECKPOINT; KINASES;
Keywords:
FHA domain; Rad53; Rad9; phosphothreonine; protein structure;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Tsai, MD Ohio State Univ, Dept Chem, 120 W 18th Ave, Columbus, OH 43210 USA Ohio State Univ 120 W 18th Ave Columbus OH USA 43210 OH 43210 USA
Citazione:
C.H. Yuan et al., "Solution structures of two FHA1-phosphothreonine peptide complexes provideinsight into the structural basis of the ligand specificity of FHA1 from yeast Rad53", J MOL BIOL, 314(3), 2001, pp. 563-575

Abstract

Rad53, a yeast checkpoint protein involved in regulating the repair of DNAdamage, 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: (SLEV)-S-188(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)PTDPLE160. Both complexes showed intermolecular NOEs predominantly between three peptideresidues (pT, +1, and +2 residues) and five FHA1 residues (S82, R83, S85, T106, and N107). Furthermore, the following interactions were implicated onthe 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 arelated 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 (C) 2001 Academic Press.

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Documento generato il 04/04/20 alle ore 02:31:22