1QVP

C terminal SH3-like domain from Diphtheria toxin Repressor residues 144-226.

1QVP の概要

• エントリーDOI: 10.2210/pdb1qvp/pdb
• 関連するPDBエントリー: 1BYM
• 分子名称: Diphtheria toxin repressor (1 entity in total)
• 機能のキーワード: repressor, dtxr, c-terminal domain, prokaryotic sh3 domain, transcription regulation, peptide-binding, gene regulation, dna binding protein
• 由来する生物種: Corynebacterium diphtheriae
• 細胞内の位置: Cytoplasm: P33120
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9659.80

構造登録者

Wylie, G.P.,Rangachari, V.,Bienkiewicz, E.A.,Marin, V.,Bhattacharya, N.,Love, J.F.,Murphy, J.R.,Logan, T.M. (登録日: 2003-08-28, 公開日: 2004-11-02, 最終更新日: 2024-05-22)

主引用文献

Wylie, G.P.,Rangachari, V.,Bienkiewicz, E.A.,Marin, V.,Bhattacharya, N.,Love, J.F.,Murphy, J.R.,Logan, T.M.
Prolylpeptide binding by the prokaryotic SH3-like domain of the diphtheria toxin repressor: a regulatory switch.
Biochemistry, 44:40-51, 2005

PubMed Abstract: Diphtheria toxin repressor (DtxR) regulates the expression of iron-sensitive genes in Corynebacterium diphtheriae, including the diphtheria toxin gene. DtxR contains an N-terminal metal- and DNA-binding domain that is connected by a proline-rich flexible peptide segment (Pr) to a C-terminal src homology 3 (SH3)-like domain. We determined the solution structure of the intramolecular complex formed between the proline-rich segment and the SH3-like domain by use of NMR spectroscopy. The structure of the intramolecularly bound Pr segment differs from that seen in eukaryotic prolylpeptide-SH3 domain complexes. The prolylpeptide ligand is bound by the SH3-like domain in a deep crevice lined by aliphatic amino acid residues and passes through the binding site twice but does not adopt a polyprolyl type-II helix. NMR studies indicate that this intramolecular complex is present in the apo-state of the repressor. Isothermal equilibrium denaturation studies show that intramolecular complex formation contributes to the stability of the apo-repressor. The binding affinity of synthetic peptides to the SH3-like domain was determined using isothermal titration calorimetry. From the structure and the binding energies, we calculated the enhancement in binding energy for the intramolecular reaction and compared it to the energetics of dimerization. Together, the structural and biophysical studies suggest that the proline-rich peptide segment of DtxR functions as a switch that modulates the activation of repressor activity.

PubMed: 15628844
DOI: 10.1021/bi048035p

実験手法

SOLUTION NMR