Crystal structure of hyperthermophilic archaeal initiation factor 5A: a homologue of eukaryotic initiation factor 5A (eIF-5A).
Crystal structure of hyperthermophilic archaeal initiation factor 5A: a homologue of eukaryotic initiation factor 5A (eIF-5A).
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DOI：
10.1093/jb/mvg011
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发表时间：
2003
影响因子：
2.7
通讯作者：
M. Yao;A. Ohsawa;S. Kikukawa;I. Tanaka;M. Kimura
中科院分区：
文献类型：
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作者：
M. Yao;A. Ohsawa;S. Kikukawa;I. Tanaka;M. Kimura
真核起始因子5A（eIF-5A）在真核生物和古细菌中普遍存在，对细胞增殖和存活至关重要。用分子置换法测定了超嗜热古细菌Pyrococcus horikoshii OT 3的eIF-5A同源物（PhoIF-5A）的晶体结构。PhoIF-5A主要由β链组成，所述β链包含两个不同的折叠结构域，N结构域（残基1-69）和C结构域（残基72-138），通过短接头肽（残基70-71）连接。N-结构域具有SH 3样桶，而C-结构域折叠成（寡核苷酸/寡糖结合）OB折叠。PhoIF-5A与来自詹氏甲烷球菌（Methanococcus jannaschii）和嗜氧热杆菌（Pyrobaculum aerophilum）的古细菌同系物的结构比较表明，N-结构域可以叠加，均方根偏差（rmsd）值分别为0.679和0.624 A，而C-结构域分别为1.824和1.329 A。一些证据表明，eIF-5A作为一种能够与蛋白质和核酸相互作用的生物调节蛋白发挥作用。静电势的表面表示表明，PhoIF-5A具有凹面，N-结构域和C-结构域之间带有带正电的残基。此外，具有羟腐胺赖氨酸修饰位点的柔性发夹环L1（残基33-41）带正电，从N结构域突出。相反，在C-结构域处的凹面的相对侧大多带负电荷。这些发现导致推测N结构域的凹面和L1环可能参与RNA结合，而C结构域凹面的相对侧可能参与蛋白质相互作用。
Eukaryotic initiation factor 5A (eIF-5A) is ubiquitous in eukaryotes and archaebacteria and is essential for cell proliferation and survival. The crystal structure of the eIF-5A homologue (PhoIF-5A) from a hyperthermophilic archaebacterium Pyrococcus horikoshii OT3 was determined at 2.0 A resolution by the molecular replacement method. PhoIF-5A is predominantly composed of beta-strands comprising two distinct folding domains, an N-domain (residues 1-69) and a C-domain (residues 72-138), connected by a short linker peptide (residues 70-71). The N-domain has an SH3-like barrel, while the C-domain folds in an (oligonucleotide/oligosaccharide binding) OB fold. Comparison of the structure of PhoIF-5A with those of archaeal homologues from Methanococcus jannaschii and Pyrobaculum aerophilum showed that the N-domains could be superimposed with root mean square deviation (rmsd) values of 0.679 and 0.624 A, while the C-domains gave higher values of 1.824 and 1.329 A, respectively. Several lines of evidence suggest that eIF-5A functions as a biomodular protein capable of interacting with protein and nucleic acid. The surface representation of electrostatic potential shows that PhoIF-5A has a concave surface with positively charged residues between the N- and C-domains. In addition, a flexible long hairpin loop, L1 (residues 33-41), with a hypusine modification site is positively charged, protruding from the N-domain. In contrast, the opposite side of the concave surface at the C-domain is mostly negatively charged. These findings led to the speculation that the concave surface and loop L1 at the N-domain may be involved in RNA binding, while the opposite side of the concave surface in the C-domain may be involved in protein interaction.