8AAZ

High resolution X-ray analysis of ATP lysozyme complex in the presence of 80 mM ATP

8AAZ の概要

• エントリーDOI: 10.2210/pdb8aaz/pdb
• 分子名称: Lysozyme, ADENOSINE-5'-TRIPHOSPHATE (3 entities in total)
• 機能のキーワード: complex, ligand binding, atp, lysozyme, hydrolase
• 由来する生物種: Gallus gallus (chicken)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15852.70

構造登録者

Zalar, M.,Curtis, R. (登録日: 2022-07-04, 公開日: 2023-01-25, 最終更新日: 2024-11-20)

主引用文献

Zalar, M.,Bye, J.,Curtis, R.
Nonspecific Binding of Adenosine Tripolyphosphate and Tripolyphosphate Modulates the Phase Behavior of Lysozyme.
J.Am.Chem.Soc., 145:929-943, 2023

PubMed Abstract: Adenosine tripolyphosphate (ATP) is a small polyvalent anion that has recently been shown to interact with proteins and have a major impact on assembly processes involved in biomolecular condensate formation and protein aggregation. However, the nature of non-specific protein-ATP interactions and their effects on protein solubility are largely unknown. Here, the binding of ATP to the globular model protein is characterized in detail using X-ray crystallography and nuclear magnetic resonance (NMR). Using NMR, we identified six ATP binding sites on the lysozyme surface, with one known high-affinity nucleic acid binding site and five non-specific previously unknown sites with millimolar affinities that also bind tripolyphosphate (TPP). ATP binding occurs primarily through the polyphosphate moiety, which was confirmed by the X-ray structure of the lysozyme-ATP complex. Importantly, ATP binds preferentially to arginine over lysine in non-specific binding sites. ATP and TPP have similar effects on solution-phase protein-protein interactions. At low salt concentrations, ion binding to lysozyme causes precipitation, while at higher salt concentrations, redissolution occurs. The addition of an equimolar concentration of magnesium to ATP does not alter ATP binding affinities but prevents lysozyme precipitation. These findings have important implications for both protein crystallization and cell biology. Crystallization occurs readily in ATP solutions outside the well-established crystallization window. In the context of cell biology, the findings suggest that ATP binds non-specifically to folded proteins in physiological conditions. Based on the nature of the binding sites identified by NMR, we propose several mechanisms for how ATP binding can prevent the aggregation of natively folded proteins.

PubMed: 36608272
DOI: 10.1021/jacs.2c09615

実験手法

X-RAY DIFFRACTION (1.27 Å)