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SARS-CoV之結構蛋白質在昆蟲細胞內之表現與純化程序之探討
Thesis

SARS-CoV之結構蛋白質在昆蟲細胞內之表現與純化程序之探討

賴家瑋
Masters, 國立清華大學, 化學工程學系
2004

Abstract

嚴重呼吸道症候群病毒 結構蛋白質 桿狀病毒 固定化金屬親和力管柱層析法 純化 SARS-CoV structural protein baculovirus immobilized metal affinity chromatograhy purification
The capsid of SARS-CoV (Severe Acute Respiratory Syndrome Coronavirus) is composed of four structural proteins, including the spike glycoprotein (S protein), small envelope protein (E protein), membrane glycoprotein (M protein) and nucleocapsid protein (N protein). These 4 structural proteins might be the antigenic determinants of SARS-CoV, thus they might be capable of inducing immune-responses against SARS-CoV. In this study, 4 recombinant baculoviruses Bac-SH, Bac-EH, Bac-MH and Bac-NH were constructed to express 4 Histidine-tagged S (rSH), E (rEH), M (rMH) and N (rNH) proteins, respectively, in insect cells. rEH, rMH and rNH expressed in Sf-9 cell were localized in the organelle, nucleus and plasma membrane, respectively. The maximum specific yield of rNH (90 μg/106 cells) was 7-fold higher than that of rEH (12.5 μg/106 cells), probably due to the variation in their localization. The differences in the intrinsic properties also resulted in the difference in the extraction process of rEH and rMH. rNH could be readily solublized by native binding buffer, and 2.75 mg rNH could be purified from 100 ml infected cells with a purifity of 90% by Immobilized Metal Affinity Chromatography (IMAC). However, rEH required the combination of a two-stage process and the use of urea for efficient extraction, and 0.66 mg rEH was purified from 200 ml infected cells with a purity of 72% by IMAC. In contrast, serious protein aggregation hindered the detection and purification of rMH. Purified rEH and rNH could be used in the development of SARS diagnostic reagents and possibly in the development of SARS vaccines.

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