A HEX-1 crystal lattice required for Woronin body function in Neurospora crassa
A HEX-1 crystal lattice required for Woronin body function in Neurospora crassa
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DOI：
10.1038/nsb910
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发表时间：
2003-04-01
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影响因子：
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通讯作者：
Swaminathan, K
中科院分区：
文献类型：
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作者：
Yuan, P;Jedd, G;Swaminathan, K
Woronin小体是丝状子囊菌（真子囊菌）特有的致密核囊泡，其功能是在细胞损伤时封闭隔孔。HEX-1蛋白自我组装形成囊泡的固体核心。在此，我们求解了HEX-1在1.8埃的晶体结构，为其自组装提供了结构基础。该结构揭示了三个促进三维蛋白质晶格形成的分子间界面的存在。与这些数据一致，自组装被分子间接触残基的突变破坏，而装配缺陷的HEX-1突变体的表达导致畸变Woronin小体的产生，这些小体具有可溶的非晶体核心。该突变体也不能补充粗神经孢子虫的hexx -1缺失，这表明hexx -1蛋白晶格是Woronin体功能所必需的。虽然hexx -1的序列和三级结构与真核起始因子5A （eIF-5A）相似，但HEX-1自组装和过氧化物酶体靶向所需的氨基酸在eIF-5A中缺失。因此，我们提出在祖先eIF-5A基因复制之后进化出了一种新的功能，这可能是真菌进化的重要一步。
The Woronin body is a dense-core vesicle specific to filamentous ascomycetes (Euascomycetes), where it functions to seal the septal pore in response to cellular damage. The HEX-1 protein self-assembles to form this solid core of the vesicle. Here, we solve the crystal structure of HEX-1 at 1.8 Angstrom, which provides the structural basis of its self-assembly. The structure reveals the existence of three intermolecular interfaces that promote the formation of a three-dimensional protein lattice. Consistent with these data, self-assembly is disrupted by mutations in intermolecular contact residues and expression of an assembly-defective HEX-1 mutant results in the production of aberrant Woronin bodies, which possess a soluble noncrystalline core. This mutant also fails to complement a hex-1 deletion in Neurospora crassa, demonstrating that the HEX-1 protein lattice is required for Woronin body function. Although both the sequence and the tertiary structure of HEX-1 are similar to those of eukaryotic initiation factor 5A (eIF-5A), the amino acids required for HEX-1 self-assembly and peroxisomal targeting are absent in eIF-5A. Thus, we propose that a new function has evolved following duplication of an ancestral eIF-5A gene and that this may define an important step in fungal evolution.