Huntingtin interacts with cystathionine β-synthase
Huntingtin interacts with cystathionine β-synthase
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DOI：
10.1093/hmg/7.3.371
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发表时间：
1998-03-01
影响因子：
3.5
通讯作者：
Jones, AL
中科院分区：
文献类型：
--
作者：
Boutell, JM;Wood, JD;Jones, AL
我们已经筛选了大鼠脑文库以鉴定在酵母双杂交系统中与亨廷顿蛋白的5 '末端（氨基酸1-171）相互作用的蛋白质，包括多聚谷氨酰胺段。我们检测到与胱硫醚β-合酶（CBS）[L-丝氨酸水解酶（添加同型半胱氨酸），EC www.example.com ]的相互作用4.2.1.22，这在体外使用在大肠杆菌中表达的His-标记的CBS证实，在酵母双杂交系统中，正常的或扩增的多聚谷氨酰胺重复序列单独都不与CBS相互作用，含有SBMA或DRPLA与正常或扩增的多聚谷氨酰胺束的构建体也不与CBS相互作用，因此CBS似乎与亨廷顿蛋白特异性结合。CBS缺乏与高胱氨酸尿症相关，已知其影响各种生理系统，包括中枢神经系统。高半胱氨酸，CBS的底物之一，已知在高胱氨酸尿症中积累并代谢为高半胱氨酸和高半胱氨酸亚磺酸盐，两者均已知为兴奋毒性氨基酸，已经表明，亨廷顿病涉及兴奋性毒性氨基酸的作用，并且这种与CBS的相互作用可能提示这种兴奋性毒性损伤的机制。
We have screened a rat brain library to identify proteins which interact with the 5'-end of huntingtin (amino acids 1-171), including the polyglutamine tract, in the yeast two-hybrid system, We detected an interaction with cystathionine beta-synthase (CBS) [L-serine hydrolyase (adding homocysteine), EC 4.2.1.22], which was confirmed in vitro using His-tagged CBS expressed in Escherichia coli, which was able to specifically bind both rat and human full-length huntingtin, Neither normal nor expanded polyglutamine repeat alone interacted with CBS in the yeast two-hybrid system and nor did constructs containing SBMA or DRPLA with normal or expanded polyglutamine tracts, CBS therefore appears to bind specifically to huntingtin. CBS deficiency is associated with homocystinuria, which is known to affect various physiological systems, including the central nervous system, Homocysteine, one of the substrates of CBS, is known to accumulate in homocystinuria and is metabolized to homocysteine and homocysteine sulphinate, both known to be excitotoxic amino acids, It has been suggested that Huntington's disease involves the action of excitotoxic amino acids and this interaction with CBS may suggest a mechanism for such excitotoxic damage.