The conserved N-terminal region of the mitotic checkpoint protein BUBR1: A putative TPR motif of high surface activity
The conserved N-terminal region of the mitotic checkpoint protein BUBR1: A putative TPR motif of high surface activity
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DOI：
10.1529/biophysj.105.063511
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发表时间：
2005-10-01
影响因子：
3.4
通讯作者：
Blundell, TL
中科院分区：
文献类型：
--
作者：
Bolanos-Garcia, VM;Beaufils, S;Blundell, TL
BUBR 1是有丝分裂纺锤体检查点的关键成分，是一种多结构域蛋白激酶，其响应于动粒张力而被激活。虽然BUB 1和BUBR 1在细胞分裂中起重要作用，但对其结构特征知之甚少。我们表明，保守的N-末端区域的BUBR 1，包括残基1 - 204，是一个球状结构域的高α-螺旋含量（约60%），稳定的pH范围4 - 9，并可能组织为一个tetratricopeptide基序重复（TPR），最接近残基16 - 181的蛋白磷酸酶5。因为后者呈现连续的两亲性凹槽并且通过结合某些脂肪酸来调节，所以我们比较了BUBR 1（1 - 204）和TPR-PP 5（16 - 181）在空气/水界面处的性质，并且发现两种蛋白质表现出相似的表面活性并且形成稳定的刚性单层。可能包含BUBR 1的几个α-螺旋的区域的缺失表明，长程相互作用对于N-末端结构域的稳定性是必不可少的。推定TPR基序的存在强烈表明BUBR 1的N-末端结构域参与直接的蛋白质-蛋白质相互作用和/或蛋白质-脂质相互作用。
BUBR1, a key component of the mitotic spindle checkpoint, is a multidomain protein kinase that is activated in response to kinetochore tension. Although BUB1 and BUBR1 play an important role in cell division, very little is known about their structural characteristics. We show that the conserved N- terminal region of BUBR1, comprising residues 1 - 204, is a globular domain of high alpha- helical content (approximate to 60%), stable in the pH range 4 - 9 and probably organized as a tetratricopeptide motif repeat ( TPR), most closely resembling residues 16 - 181 of protein phosphatase 5. Because the latter presents a continuous amphipathic groove and is regulated by binding certain fatty acids, we compared the properties of BUBR1( 1 - 204) and TPR- PP5 ( 16 - 181) at air/ water interfaces and found that both proteins exhibited a similar surface activity and formed stable, rigid monolayers. The deletion of a region that probably comprises several a- helices of BUBR1 indicates that long- range interactions are essential for the stability of the N- terminal domain. The presence of the putative TPR motif strongly suggests that the N- terminal domain of BUBR1 is involved in direct protein- protein interactions and/ or protein- lipid interactions.