Nickel Binding to the c-Src SH3 Domain Facilitates Crystallization.

IF 2.5 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Protein and Peptide Letters Pub Date : 2025-01-01 DOI:10.2174/0109298665417324250929120040

Xander Calicdan, Oriana S Fisher, Byung Hak Ha, Titus J Boggon, Amy L Stiegler

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引用次数: 0

Abstract

Introduction: Numerous X-ray crystal structures of the c-Src SH3 domain have provided a large sampling of atomic-level information for this important signaling domain. Multiple crystal forms have been reported, with variable crystal lattice contacts and chemical crystallization conditions.

Materials and methods: We crystallized the c-Src SH3 domain in a crystallization buffer containing NiCl₂.

Results: A unique crystal structure of the Src SH3 domain in the trigonal space group H32 is determined to 1.45 Å resolution. Crystal packing and anomalous scattering reveal that this crystal form is mediated by two ordered nickel ions provided by the crystallization buffer. Nickel coordination occurs in a 2:2 stoichiometry, which dimerizes two SH3 domain monomers across a pseudo-twofold rotation axis and involves the native N-terminal c-Src SH3 amino acid sequence, a surface-exposed histidine residue, and ordered water molecules.

Discussion: This study provides an example of metal-mediated crystallization and metal binding by N-terminal protein residues, contrasting with the Amino-Terminal Copper and Nickel Binding (ATCUN) motif.

Conclusion: Alternative avenues help widen the potential for future crystallography-based studies of the c-Src SH3 domain.

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镍与c-Src SH3结构域结合有利于结晶。

c-Src SH3结构域的大量x射线晶体结构为这一重要的信号结构域提供了大量的原子级信息采样。已经报道了多种晶体形式，具有可变的晶格接触和化学结晶条件。材料和方法：我们在含有NiCl2的结晶缓冲液中结晶c-Src SH3结构域。结果：在三角形空间群H32中确定了Src SH3结构域的独特晶体结构，分辨率为1.45 Å。晶体堆积和异常散射表明，这种晶体形式是由结晶缓冲液提供的两个有序镍离子介导的。镍以2:2的化学计量发生配位，两个SH3结构域单体在伪双轴上二聚，涉及天然n端c-Src SH3氨基酸序列，表面暴露的组氨酸残基和有序的水分子。讨论：本研究提供了一个金属介导结晶和n端蛋白残基金属结合的例子，与氨基端铜镍结合（ATCUN）基序进行了对比。结论：其他途径有助于扩大未来基于c-Src SH3结构域晶体学研究的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Protein and Peptide Letters 生物-生化与分子生物学

CiteScore

2.90

自引率

0.00%

发文量

审稿时长

2 months

期刊介绍： Protein & Peptide Letters publishes letters, original research papers, mini-reviews and guest edited issues in all important aspects of protein and peptide research, including structural studies, advances in recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, and drug design. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallization and preliminary structure determination of biologically important proteins are considered only if they include significant new approaches or deal with proteins of immediate importance, and preliminary structure determinations of biologically important proteins. Purely theoretical/review papers should provide new insight into the principles of protein/peptide structure and function. Manuscripts describing computational work should include some experimental data to provide confirmation of the results of calculations. Protein & Peptide Letters focuses on: Structure Studies Advances in Recombinant Expression Drug Design Chemical Synthesis Function Pharmacology Enzymology Conformational Analysis Immunology Biotechnology Protein Engineering Protein Folding Sequencing Molecular Recognition Purification and Analysis