Zinc- and pH-dependent conformational transition in a putative interdornain linker region of the influenza virus matrix protein M1
Zinc- and pH-dependent conformational transition in a putative interdornain linker region of the influenza virus matrix protein M1
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DOI：
10.1021/bi027176t
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发表时间：
2003-02-25
期刊：
影响因子：
2.9
通讯作者：
Takeuchi, H
中科院分区：
文献类型：
--
作者：
Okada, A;Miura, T;Takeuchi, H
甲型流感病毒的基质蛋白M1在病毒包膜下形成一个外壳，并通过与其他病毒组分相互作用维持病毒体结构。在病毒感染的早期阶段，病毒粒子内部酸化后M1的结构变化被认为是病毒脱壳的关键步骤。我们研究了一个28-mer肽（M1Lnk）的结构，代表一个假定的接头区域之间的N-和C-末端结构域的M1通过使用圆二色谱，拉曼，和吸收光谱。M1Lnk在轻度疏水环境中呈现α-螺旋结构，与pH值无关，这与M1的N-末端片段在pH值7和4时的X射线晶体结构一致。另一方面，在Zn 2+的存在下，M1Lnk在中性pH下采取部分未折叠的构象，在肽的中心部分具有两个Cys残基和两个His残基与Zn 2+离子的四面体配位。在酸化时，肽释放Zn 2+离子并重新折叠成富含α-螺旋的结构，其过渡中点在pH 5.9。M1Lnk的pH依赖性构象转变强烈表明，在Zn 2+存在下，M1的结构域间连接区也经历了pH依赖性的展开-重折叠转变。一个小的，但重要的一部分M1蛋白结合到病毒粒子中的Zn 2+，和Zn 2+结合的M1分子可能发挥特殊的作用，通过改变病毒粒子内部酸化后的N-和C-末端结构域的处置在病毒脱壳。
The matrix protein M1 of influenza A virus forms a shell beneath the viral envelope and sustains the virion architecture by interacting with other viral components. A structural change of M1 upon acidification of the virion interior in an early stage of virus infection is considered to be a key step to virus uncoating. We examined the structure of a 28-mer peptide (M1Lnk) representing a putative linker region between the N- and C-terminal domains of M1 by using circular dichroism, Raman, and absorption spectroscopy. M1Lnk assumes an alpha-helical structure in a mildly hydrophobic environment irrespective of pH, being consistent with the X-ray crystal structures of an N-terminal fragment of M1 at pH 7 and 4. In the presence of Zn2+, on the other hand, M1Lnk takes a partially unfolded conformation at neutral pH with a tetrahedral coordination of two Cys residues and two His residues to a Zn2+ ion in the central part of the peptide. Upon acidification, the peptide releases the Zn2+ ion and refolds into the alpha-helix-rich structure with a midpoint of transition at pH 5.9. The pH-dependent conformational transition of M1Lnk strongly suggests that the interdomain linker region of M1 also undergoes a pH-dependent unfolding-refolding transition in the presence of Zn2+. A small but significant portion of the M1 protein is bound to Zn2+ in the virion, and the Zn2+-bound M1 molecule may play a special role in virus uncoating by changing the disposition of the N- and C-terminal domains upon acidification of the virion interior.