小麦胚芽凝集素及其分离结构域结构稳定性的解码机制:热量测定、核磁共振和 MD 模拟联合研究。

IF 4.5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Protein Science Pub Date : 2024-06-01 DOI:10.1002/pro.5020
Jorge Luis Medrano-Cerano, Luis Fernando Cofas-Vargas, Eduardo Leyva, Jesús Antonio Rauda-Ceja, Mateo Calderón-Vargas, Patricia Cano-Sánchez, Gustavo Titaux-Delgado, Carolina Monserrath Melchor-Meneses, Andrés Hernández-Arana, Federico Del Río-Portilla, Enrique García-Hernández
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引用次数: 0

摘要

小麦胚芽凝集素(WGA)因其与碳水化合物的选择性结合及其穿越生物膜的能力而具有作为口服给药剂的潜力。在这项研究中,我们采用差示扫描量热法和分子动力学模拟全面描述了完整凝集素及其四个分离结构域的热折叠过程。此外,我们还展示了三个结构域的核磁共振结构,这三个结构域之前一直缺乏分离形式的实验结构。我们的研究结果提供了对支配完整凝集素复杂解折机制的能量和结构因素的集体理解,揭示了每个结构域在这一过程中所扮演的特定角色。分析表明,结构域之间的协同作用可以忽略不计,相反,二聚体解离与较易变结构域的展开之间存在着显著的耦合关系。通过比较主要的相互作用,我们合理地解释了各结构域之间的稳定性差异。了解 WGA 的结构稳定性为加强药物递送策略开辟了途径,同时也凸显了它作为胃肠道环境载体的潜力。
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Decoding the mechanism governing the structural stability of wheat germ agglutinin and its isolated domains: A combined calorimetric, NMR, and MD simulation study.

Wheat germ agglutinin (WGA) demonstrates potential as an oral delivery agent owing to its selective binding to carbohydrates and its capacity to traverse biological membranes. In this study, we employed differential scanning calorimetry and molecular dynamics simulations to comprehensively characterize the thermal unfolding process of both the complete lectin and its four isolated domains. Furthermore, we present the nuclear magnetic resonance structures of three domains that were previously lacking experimental structures in their isolated forms. Our results provide a collective understanding of the energetic and structural factors governing the intricate unfolding mechanism of the complete agglutinin, shedding light on the specific role played by each domain in this process. The analysis revealed negligible interdomain cooperativity, highlighting instead significant coupling between dimer dissociation and the unfolding of the more labile domains. By comparing the dominant interactions, we rationalized the stability differences among the domains. Understanding the structural stability of WGA opens avenues for enhanced drug delivery strategies, underscoring its potential as a promising carrier throughout the gastrointestinal environment.

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来源期刊
Protein Science
Protein Science 生物-生化与分子生物学
CiteScore
12.40
自引率
1.20%
发文量
246
审稿时长
1 months
期刊介绍: Protein Science, the flagship journal of The Protein Society, is a publication that focuses on advancing fundamental knowledge in the field of protein molecules. The journal welcomes original reports and review articles that contribute to our understanding of protein function, structure, folding, design, and evolution. Additionally, Protein Science encourages papers that explore the applications of protein science in various areas such as therapeutics, protein-based biomaterials, bionanotechnology, synthetic biology, and bioelectronics. The journal accepts manuscript submissions in any suitable format for review, with the requirement of converting the manuscript to journal-style format only upon acceptance for publication. Protein Science is indexed and abstracted in numerous databases, including the Agricultural & Environmental Science Database (ProQuest), Biological Science Database (ProQuest), CAS: Chemical Abstracts Service (ACS), Embase (Elsevier), Health & Medical Collection (ProQuest), Health Research Premium Collection (ProQuest), Materials Science & Engineering Database (ProQuest), MEDLINE/PubMed (NLM), Natural Science Collection (ProQuest), and SciTech Premium Collection (ProQuest).
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