保守痘病毒入口融合复合体蛋白组分A21的2.3 Å结构

IF 4.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Molecular Biology Pub Date : 2025-03-19 DOI:10.1016/j.jmb.2025.169097

Ulrike S. Diesterbeck , Liya A. Muslinkina , Apostolos G. Gittis , Kavita Singh , Bernard Moss , David N. Garboczi

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引用次数: 0

摘要

痘病毒的特殊之处在于，它有一个由11个保守蛋白组成的入口融合复合体（EFC），嵌入成熟病毒粒子的膜中。为了了解EFC的功能，人们已经做出了广泛的努力来确定其组成部分的结构和作用，到目前为止，已经确定了11种蛋白质中的9种的结构。在这里，我们报道了第10个EFC蛋白A21的晶体结构，它由两个α-螺旋组成，由两个保守的二硫键稳定的扭曲反平行β-片。每个A21环的稳定性是由主链原子和几个高度保守的残基之间的氢键提供的，这使得A21及其同源物的整体折叠具有进化变化的弹性。基于AlphaFold建模和系统发育分析，我们发现A21高度保守的n端跨膜结构域和c端α-螺旋结构使A21能够整合到EFC中，并主要与G3/L5亚复合物和EFC中最小的组分O3蛋白相互作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

The 2.3 Å Structure of A21, a Protein Component of the Conserved Poxvirus Entry-Fusion Complex

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The 2.3 Å Structure of A21, a Protein Component of the Conserved Poxvirus Entry-Fusion Complex

Poxviruses are exceptional in having an entry-fusion complex (EFC) consisting of eleven conserved proteins embedded in the membrane of mature virions. With the goal of understanding the function of the EFC, extensive efforts have been made to determine the structures and roles of its components, and to date, structures have been determined for nine of the eleven proteins. Here, we report the crystal structure of A21, the 10th EFC protein, comprising two α-helices clasping a twisted antiparallel β-sheet stabilized by two conserved disulfide bonds. The stability of each of the three A21 loops is provided by hydrogen bonds between main-chain atoms and several highly conserved residues, making the overall fold of A21 and its orthologs resilient to evolutionary change. Based on AlphaFold modeling and phylogenetic analysis of A21, we suggest that its highly conserved N-terminal transmembrane domain and C-terminal α-helix enable A21 integration into EFC, where it primarily interacts with the G3/L5 subcomplex and the smallest of EFC components, the O3 protein.

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来源期刊

Journal of Molecular Biology 生物-生化与分子生物学

CiteScore

11.30

自引率

1.80%

发文量

412

审稿时长

28 days

期刊介绍： Journal of Molecular Biology (JMB) provides high quality, comprehensive and broad coverage in all areas of molecular biology. The journal publishes original scientific research papers that provide mechanistic and functional insights and report a significant advance to the field. The journal encourages the submission of multidisciplinary studies that use complementary experimental and computational approaches to address challenging biological questions. Research areas include but are not limited to: Biomolecular interactions, signaling networks, systems biology; Cell cycle, cell growth, cell differentiation; Cell death, autophagy; Cell signaling and regulation; Chemical biology; Computational biology, in combination with experimental studies; DNA replication, repair, and recombination; Development, regenerative biology, mechanistic and functional studies of stem cells; Epigenetics, chromatin structure and function; Gene expression; Membrane processes, cell surface proteins and cell-cell interactions; Methodological advances, both experimental and theoretical, including databases; Microbiology, virology, and interactions with the host or environment; Microbiota mechanistic and functional studies; Nuclear organization; Post-translational modifications, proteomics; Processing and function of biologically important macromolecules and complexes; Molecular basis of disease; RNA processing, structure and functions of non-coding RNAs, transcription; Sorting, spatiotemporal organization, trafficking; Structural biology; Synthetic biology; Translation, protein folding, chaperones, protein degradation and quality control.