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凝集素学 4.0:改变模块化(半)凝集素展示用于功能分析和生物医学应用。

Lectinology 4.0: Altering modular (ga)lectin display for functional analysis and biomedical applications.

机构信息

Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, Veterinärstr. 13, 80539 Munich, Germany.

Institute of Pathology, Department of Applied Tumor Biology, Faculty of Medicine, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.

出版信息

Biochim Biophys Acta Gen Subj. 2019 May;1863(5):935-940. doi: 10.1016/j.bbagen.2019.03.005. Epub 2019 Mar 6.

DOI:10.1016/j.bbagen.2019.03.005
PMID:30851406
Abstract

BACKGROUND

Recognition of glycans by lectins is emerging as (patho)physiologically broadly used mode of cellular information transfer. Whereas the direct ligand-receptor contact is often already thoroughly characterized, the functional relevance of aspects of architecture such as modular design and valence of lectins is less well defined.

SCOPE OF REVIEW

Following an introduction to modular lectin design, three levels of methodology are then reviewed that delineate lectin structure-activity relationships beyond glycan binding, with emphasis on domain shuffling.

MAJOR CONCLUSIONS

Engineering of variants by modular transplantation facilitates versatile Nature-inspired design switches and access to new combinations with translational potential, as exemplified for human adhesion/growth-regulatory galectins.

GENERAL SIGNIFICANCE

To gain an understanding of the functional significance of natural variations in quaternary structure and modular design within a protein family is a current challenge. Strategic application of methods of the described phases is a means to respond to this challenge.

摘要

背景

凝集素识别聚糖作为(病理)生理上广泛应用的细胞信息传递模式正在出现。虽然直接的配体-受体接触通常已经得到了充分的描述,但凝集素的结构如模块设计和价数等方面的功能相关性定义得还不够清楚。

综述范围

在介绍了模块化凝集素设计之后,然后回顾了三种方法学层次,这些方法学层次描绘了除糖结合之外的凝集素结构-活性关系,重点是结构域改组。

主要结论

通过模块化移植工程变体促进了多功能的基于自然的设计转换,并获得了具有转化潜力的新组合,例如人类粘附/生长调节半乳糖凝集素。

一般意义

了解蛋白质家族中四级结构和模块设计的自然变异的功能意义是当前的挑战。描述阶段的方法的策略性应用是应对这一挑战的一种手段。

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