Interaction of the Wilson disease protein with cellular proteins = 윌슨 단백질과 세포내 다른 단백질과의 상호작용

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Wilson disease(WD) is an autosomal recessive disorder of copper transport. Its general characteristics are defective biliary excretion of copper and impairment in the incorporation of copper in ceruloplasmin. The product of the WD gene is a copper transporting P-type ATPase (ATP7B). The ATP7B gene has 21 exons and encodes a protein of 1465 aminoacids. The ATP7B protein is localized to trans-Golgi network under steady state condition. An increase in the copper concentration resulted in the rapid movement to cytoplasmic vesicular compartments. This copper-dependent cellular redistribution of the ATP7B protein is also a reversible process. The molecular mechanism underlying the copper-induced changes in the subcellular distribution of the ATP7B protein is unknown. In this study, we used LexA Yeast-two-hybrid system to screening cytosolic protein which interacts with Wilson protein, affecting copper dependent trafficking of Wilson protein. In this experiment, we found that ATP binding loop specifically interacts with a polypeptide similar to aspartoacylase(AspA). The cDNA was not complete open reading frame, and we could not identify N-terminus. It encoded 212aa and showed 44% identity with aspartoacylase(AspA). Asparto-acylase(N-acetyl-L-aspartate amidohydrolase) specifically hydrolases N-acetyl-L-aspartic acid(NAA) to aspartate and acetate. The invariable His21 and Glu285 residues involved in the catalysis are present in the consensus sequence motifs, GGTHGNE and VNEAAYY. AspA-H also has equivalent Glu in INEAAYY. Because its N- terminus was not complete, we could not identify the motif including His. AspA is membrane associated protein and The purified AspA activity was enhanced by divalent cations. And the metal binding motifs of CuBD from the wilson protein have affinities to divalent cation. We could inferr that there could be a functional relationship between the AspA homologue and the Wilson protein, if AspA-H has AspA activity. To understand the relation...
Advisors
Yoo, Ook-Joonresearcher유욱준researcher
Description
한국과학기술원 : 생물과학과,
Publisher
한국과학기술원
Issue Date
2000
Identifier
158692/325007 / 000983124
Language
eng
Description

학위논문(석사) - 한국과학기술원 : 생물과학과, 2000.2, [ vi, 53 p. ]

Keywords

Wilson disease; 윌슨씨 병; Yeast two hybrid

URI
http://hdl.handle.net/10203/27892
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=158692&flag=dissertation
Appears in Collection
BS-Theses_Master(석사논문)
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