近日，德国马克斯·普朗克生物化学研究所教授John A. G. Briggs及其研究组报道了保守的HIV-1间隔肽2触发基质晶格成熟。2025年2月26日，国际知名学术期刊《自然》发表了这一成果。

在这里，研究团队发现释放的间隔肽2 （SP2）是一种功能未知的保守肽，位于MA下游约300个残基处，与MA结合诱导结构成熟。通过对MA的高分辨率体内结构测定，该课题组人员发现MA并没有像之前认为的那样将脂质结合到侧袋中，而是将SP2作为稳定成熟晶格的蛋白质-蛋白质界面的一个组成部分结合。对Gag切割位点突变体的分析表明，SP2的释放是MA成熟所必需的，小组证明了SP2足以在体外诱导纯化的MA在脂质单层上成熟。SP2触发的MA成熟与病毒更快地与靶细胞融合有关。他们的研究结果揭示了两种HIV-1成分之间一种新的、意想不到的相互作用，提供了成熟MA的高分辨率结构，建立了MA结构成熟的触发机制，并为SP2肽分配了功能。

据悉，人类免疫缺陷病毒1型（HIV-1）的病毒颗粒以未成熟的、非感染性的形式释放。主要结构多蛋白Gag进入功能域的蛋白水解裂解诱导重排成成熟的感染病毒粒子。在未成熟的病毒颗粒中，Gag膜结合结构域（MA）形成六聚体蛋白质晶格，并在裂解后发生结构转变，形成一个独特的成熟的MA晶格。MA晶格成熟的机制尚不清楚。

附：英文原文

Title: The conserved HIV-1 spacer peptide 2 triggers matrix lattice maturation

Author: Stacey, James C. V., Hrebk, Dominik, Nand, Elizabeth, Shetty, Snehith Dyavari, Qu, Kun, Boicu, Marius, Anders-sswein, Maria, Uchil, Pradeep D., Dick, Robert A., Mothes, Walther, Krusslich, Hans-Georg, Mller, Barbara, Briggs, John A. G.

Issue&Volume: 2025-02-26

Abstract: The virus particles of human immunodeficiency virus type 1 (HIV-1) are released in an immature, non-infectious form. Proteolytic cleavage of the main structural polyprotein Gag into functional domains induces rearrangement into mature, infectious virions. In immature virus particles, the Gag membrane-binding domain, MA, forms a hexameric protein lattice that undergoes structural transition, following cleavage, into a distinct, mature MA lattice1. The mechanism of MA lattice maturation is unknown. Here we show that released spacer peptide 2 (SP2), a conserved peptide of unknown function situated about 300 residues downstream of MA, binds MA to induce structural maturation. By high-resolution in-virus structure determination of MA, we show that MA does not bind lipid into a side pocket as previously thought1, but instead binds SP2 as an integral part of the protein–protein interfaces that stabilize the mature lattice. Analysis of Gag cleavage site mutants showed that SP2 release is required for MA maturation, and we demonstrate that SP2 is sufficient to induce maturation of purified MA on lipid monolayers in vitro. SP2-triggered MA maturation correlated with faster fusion of virus with target cells. Our results reveal a new, unexpected interaction between two HIV-1 components, provide a high-resolution structure of mature MA, establish the trigger of MA structural maturation and assign function to the SP2 peptide.

DOI: 10.1038/s41586-025-08624-9

Source: https://www.nature.com/articles/s41586-025-08624-9