Stability of HA2 Prefusion Structure and pH-Induced Conformational Changes in the HA2 Domain of H3N2 Hemagglutinin,Biochemistry

当前位置： X-MOL 学术 › Biochemistry › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Stability of HA2 Prefusion Structure and pH-Induced Conformational Changes in the HA2 Domain of H3N2 Hemagglutinin
Biochemistry ( IF 2.9 ) Pub Date : 2021-08-26 , DOI: 10.1021/acs.biochem.1c00551
Micah W Eller ₁ , Hew Ming Helen Siaw ₁ , R Brian Dyer ₁

Affiliation

Influenza hemagglutinin is the fusion protein that mediates fusion of the viral and host membranes through a large conformational change upon acidification in the developing endosome. The “spring-loaded” model has long been used to describe the mechanism of hemagglutinin and other type 1 viral glycoproteins. This model postulates a metastable conformation of the HA2 subunit, caged from adopting a lower-free energy conformation by the HA1 subunit. Here, using a combination of biochemical and spectroscopic methods, we study a truncated construct of HA2 (HA2*, lacking the transmembrane domain) recombinantly expressed in Escherichia coli as a model for HA2 without the influence of HA1. Our data show that HA2* folds into a conformation like that of HA2 in full length HA and forms trimers. Upon acidification, HA2* undergoes a conformational change that is consistent with the change from pre- to postfusion HA2 in HA. This conformational change is fast and occurs on a time scale that is not consistent with aggregation. These results suggest that the prefusion conformation of HA2 is stable and the change to the postfusion conformation is due to protonation of HA2 itself and not merely uncaging by HA1.

中文翻译：

H3N2 血凝素 HA2 结构域的 HA2 预融合结构的稳定性和 pH 诱导的构象变化

流感血凝素是一种融合蛋白，通过发育中的内体酸化时发生大的构象变化来介导病毒和宿主膜的融合。 “弹簧加载”模型长期以来一直被用来描述血凝素和其他 1 型病毒糖蛋白的机制。该模型假设 HA2 亚基具有亚稳态构象，而 HA1 亚基无法采用较低自由能构象。在这里，我们结合生化和光谱方法，研究了在大肠杆菌中重组表达的截短的 HA2 构建体（HA2*，缺乏跨膜结构域），作为 HA2 的模型，不受 HA1 的影响。我们的数据表明，HA2* 折叠成类似于全长 HA 中 HA2 的构象并形成三聚体。酸化后，HA2* 会发生构象变化，这与 HA 中融合前与融合后 HA2 的变化一致。这种构象变化很快，并且发生的时间尺度与聚集不一致。这些结果表明HA2的融合前构象是稳定的，融合后构象的变化是由于HA2本身的质子化而不仅仅是HA1的解笼锁。

更新日期：2021-09-07

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11