Atomic structures of closed and open influenza B M2 proton channel reveal the conduction mechanism.,Nature Structural & Molecular Biology

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Atomic structures of closed and open influenza B M2 proton channel reveal the conduction mechanism.
Nature Structural & Molecular Biology ( IF 12.5 ) Pub Date : 2020-02-03 , DOI: 10.1038/s41594-019-0371-2
Venkata S Mandala ₁ , Alexander R Loftis ₁ , Alexander A Shcherbakov ₁ , Bradley L Pentelute ₁ , Mei Hong ₁

Affiliation

The influenza B M2 (BM2) proton channel is activated by acidic pH to mediate virus uncoating. Unlike influenza A M2 (AM2), which conducts protons with strong inward rectification, BM2 conducts protons both inward and outward. Here we report 1.4- and 1.5-Å solid-state NMR structures of the transmembrane domain of the closed and open BM2 channels in a phospholipid environment. Upon activation, the transmembrane helices increase the tilt angle by 6° and the average pore diameter enlarges by 2.1 Å. BM2 thus undergoes a scissor motion for activation, which differs from the alternating-access motion of AM2. These results indicate that asymmetric proton conduction requires a backbone hinge motion, whereas bidirectional conduction is achieved by a symmetric scissor motion. The proton-selective histidine and gating tryptophan in the open BM2 reorient on the microsecond timescale, similar to AM2, indicating that side chain dynamics are the essential driver of proton shuttling.

中文翻译：

封闭和开放的乙型流感M2质子通道的原子结构揭示了传导机制。

B 型流感 M2 (BM2) 质子通道被酸性 pH 值激活，介导病毒脱壳。与甲型流感 M2（AM2）以强向内整流方式传导质子不同，BM2 既向内又向外传导质子。在这里，我们报告了磷脂环境中封闭和开放 BM2 通道跨膜域的 1.4 和 1.5 Å 固态 NMR 结构。激活后，跨膜螺旋的倾斜角增加 6°，平均孔径扩大 2.1 Å。因此，BM2 经历剪刀运动来激活，这与 AM2 的交替访问运动不同。这些结果表明，不对称质子传导需要主链铰链运动，而双向传导是通过对称剪刀运动实现的。开放BM2中的质子选择性组氨酸和门控色氨酸在微秒时间尺度上重新定向，类似于AM2，表明侧链动力学是质子穿梭的重要驱动力。

更新日期：2020-02-03

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