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Structural insights into the recognition of phosphorylated Hop1 by Mek1
Changlin Xie1, Chao He2, Yiyang Jiang3
1High Magnetic Field Laboratory, Chinese Academy of Sciences, 50 Shushanhu Road, Hefei, Anhui 230031, People's Republic of China.
Abstract:
The FHA domain-containing protein Mek1 is a meiosis-specific kinase that is involved in the regulation of interhomolog recombination in meiosis in Saccharomyces cerevisiae. The recruitment and activation of Mek1 require the phosphorylation of the chromosome axis protein Hop1 at Thr318 (pT318), which is necessary for recognition by the Mek1 FHA domain. Here, crystal structures of the Mek1 FHA domain in the apo state and in complex with the Hop1 pT318 peptide are presented, demonstrating that the hydrophobic residues Phe320 and Val321 at the pT+2 and pT+3 positions in the ligand contribute to the preferential recognition. It was further found that in Schizosaccharomyces pombe Mek1 FHA binds both pT15 in its N-terminal SQ/TQ cluster domain (SCD) and pT270 in the Hop1 SCD. The results revealed the structural basis for the preferential recognition of phosphorylated Hop1 by Mek1 in S. cerevisiae and facilitate the understanding of the interaction between the S. pombe Mek1 FHA domain and its binding targets.
Insights
Researchers elucidated how the Mek1 kinase recognizes phosphorylated Hop1 protein during meiosis. Crystal structures reveal specific hydrophobic residues crucial for this interaction, enhancing understanding of recombination regulation in yeast.
Area of Science:
- Molecular Biology
- Yeast Genetics
- Structural Biology
Background:
- Mek1 is a meiosis-specific kinase regulating interhomolog recombination in Saccharomyces cerevisiae.
- Mek1 activation depends on phosphorylated Hop1 (pT318), recognized by the Mek1 FHA domain.
Purpose of the Study:
- To determine the structural basis for Mek1 FHA domain recognition of phosphorylated Hop1.
- To investigate Mek1 FHA domain interactions in both S. cerevisiae and Schizosaccharomyces pombe.
Main Methods:
- X-ray crystallography was used to obtain structures of the Mek1 FHA domain.
- Complex structures were determined with a Hop1 pT318 peptide.
Main Results:
- Crystal structures revealed the Mek1 FHA domain in apo and peptide-bound states.
- Hydrophobic residues Phe320 and Val321 in Hop1 peptide are key for Mek1 FHA recognition.
- In S. pombe, Mek1 FHA binds phosphorylated sites in both Mek1 and Hop1 SQ/TQ cluster domains.
Conclusions:
- The study provides structural insights into Mek1-Hop1 interaction specificity in S. cerevisiae.
- Understanding these interactions aids in comprehending Mek1 function and its binding targets in different yeast species.
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