3PO8

Structural and functional analysis of phosphothreonine-dependent FHA domain interactions

3PO8 の概要

• エントリーDOI: 10.2210/pdb3po8/pdb
• 関連するPDBエントリー: 3POA
• 分子名称: Putative uncharacterized protein TB39.8, PHOSPHATE ION (3 entities in total)
• 機能のキーワード: fha domain, synthetic peptide, peptide binding protein
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11042.06

構造登録者

Pennell, S.,Smerdon, S.J. (登録日: 2010-11-22, 公開日: 2011-01-26, 最終更新日: 2024-03-20)

主引用文献

Pennell, S.,Westcott, S.,Ortiz-Lombardia, M.,Patel, D.,Li, J.,Nott, T.J.,Mohammed, D.,Buxton, R.S.,Yaffe, M.B.,Verma, C.,Smerdon, S.J.
Structural and functional analysis of phosphothreonine-dependent FHA domain interactions
Structure, 18:1587-1595, 2010

PubMed Abstract: FHA domains are well established as phospho-dependent binding modules mediating signal transduction in Ser/Thr kinase signaling networks in both eukaryotic and prokaryotic species. Although they are unique in binding exclusively to phosphothreonine, the basis for this discrimination over phosphoserine has remained elusive. Here, we attempt to dissect overall binding specificity at the molecular level. We first determined the optimal peptide sequence for Rv0020c FHA domain binding by oriented peptide library screening. This served as a basis for systematic mutagenic and binding analyses, allowing us to derive relative thermodynamic contributions of conserved protein and peptide residues to binding and specificity. Structures of phosphopeptide-bound and uncomplexed Rv0020c FHA domain then directed molecular dynamics simulations which show how the extraordinary discrimination in favor of phosphothreonine occurs through formation of additional hydrogen-bonding networks that are ultimately stabilized by van der Waals interactions of the phosphothreonine γ-methyl group with a conserved pocket on the FHA domain surface.

PubMed: 21134638
DOI: 10.1016/j.str.2010.09.014

実験手法

X-RAY DIFFRACTION (1.5 Å)