Human Rhinovirus 2 2Apro Recognition of Eukaryotic Initiation Factor 4GI
Human Rhinovirus 2 2Apro Recognition of Eukaryotic Initiation Factor 4GI
复制标题
人鼻病毒2 2Apro识别真核起始因子4GI
DOI：
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发表时间：
2003
影响因子：
4.8
通讯作者：
T. Skern
中科院分区：
文献类型：
--
作者：
Nicole Foeger;Eva M. Schmid;T. Skern
人鼻病毒2型2A蛋白酶（2Apro）是一种半胱氨酸蛋白酶，具有独特的糜蛋白酶样折叠。在病毒复制过程中，2Apro通过在其自身的N末端和前一个蛋白VP 1的C末端之间进行切割来进行自我加工。随后，2Apro切割细胞蛋白的两种同种型，真核起始因子（eIF）4G。我们以前已经证明，HRV 2 2Apro可以直接结合eIF 4G亚型。在这里，我们使用eIF 4GI的缺失突变体证明了HRV 2 2Apro需要eIF 4GI氨基酸600-674来结合;然而，不需要切割位点的氨基酸Arg 681 ↓ Gly。通过定点诱变鉴定eIF 4GI的HRV 2 2Apro结合结构域。具体而言，突变Leu 17 → Arg和Asp 35 → Glu严重损害了兔网织红细胞裂解物中的HRV 2 2Apro结合，从而损害了eIF 4GI的加工;然而，自我加工不受影响。丙氨酸扫描分析进一步鉴定了含有残基Tyr 32、Ser 33和Ser 34的环对于eIF 4GI结合是重要的。虽然Asp 35是催化三联体的一部分，但大多数eIF 4GI结合结构域位于其他胰凝乳蛋白酶样酶不存在的独特外位点结构中，并且与底物结合裂缝不同。外切位点代表了一种新的毒力决定因素，可能允许开发针对HRV 2 Apro的特异性抑制剂。
The 2A proteinase (2Apro) of human rhinovirus 2 is a cysteine proteinase with a unique chymotrypsin-like fold. During viral replication, 2Apro performs self-processing by cleaving between its own N terminus and the C terminus of the preceding protein, VP1. Subsequently, 2Apro cleaves the two isoforms of the cellular protein, eukaryotic initiation factor (eIF) 4G. We have previously shown that HRV2 2Apro can directly bind to eIF4G isoforms. Here we demonstrate using deletion mutants of eIF4GI that HRV2 2Apro requires eIF4GI amino acids 600–674 for binding; however, the amino acids at the cleavage site, Arg681 ↓ Gly, are not required. The HRV2 2Apro binding domain for eIF4GI was identified by site-directed mutagenesis. Specifically, mutations Leu17 → Arg and Asp35 → Glu severely impaired HRV2 2Apro binding and thus processing of eIF4GI in rabbit reticulocyte lysates; self-processing, however, was not affected. Alanine scanning analysis further identified the loop containing residues Tyr32, Ser33, and Ser34 as important for eIF4GI binding. Although Asp35 is part of the catalytic triad, most of the eIF4GI binding domain lies in a unique exosite structure absent from other chymotrypsin-like enzymes and is distinct from the substrate binding cleft. The exosite represents a novel virulence determinant that may allow the development of specific inhibitors for HRV2 2Apro.
影响因子：
56.9
作者：
RYDEL, TJ;RAVICHANDRAN, KG;FENTON, JW
通讯作者：
FENTON, JW
人类蛋白质合成起始因子 eIF-4 γ 的氨基酸序列。
DOI：
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发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Yan,R;Rychlik,W;Etchison,D;Rhoads,RE
通讯作者：
Rhoads,RE