Crystal structure of rat Bcl-x(L) - Implications for the function of the Bcl-2 protein family
Crystal structure of rat Bcl-x(L) - Implications for the function of the Bcl-2 protein family
复制标题
DOI：
10.1074/jbc.272.44.27886
复制
发表时间：
1997-10-31
影响因子：
4.8
通讯作者：
Morikawa, K
中科院分区：
文献类型：
--
作者：
Aritomi, M;Kunishima, N;Morikawa, K
Bcl-x（L）是Bcl-2蛋白家族的成员，其调节细胞凋亡。制备重组大鼠Bcl-x（L）产生两种形式，一种在-Asn-Gly-序列处脱酰胺以产生异丙二酸酯，另一种不脱酰胺。两种形式的晶体结构表明，它们都采用了基本相同的骨架结构，类似于人类Bcl-x（L）的折叠：三层，每层两个α-螺旋，一端被两个短螺旋封端。这两种形式都有一个长的无序区域，其中包含潜在的脱酰胺位点。的分子结构表现出低水平的螺旋间相互作用，存在三个空腔，和一个显着的疏水性裂缝周围的墙壁富含碱性残基。这些独特的结构特征可能有利于其适应膜或可能的重排，以调节同源/异源二聚化。基于Bcl-x（L）结构的Bcl-2和Bax的同源建模表明Bax具有最强的膜插入潜力。此外，我们发现了一个可能的接口与非Bcl-2家族成员的蛋白质，如CED-4同源物的相互作用。
Bcl-x(L) is a member of the Bcl-2 protein family, which regulates apoptosis. Preparation of recombinant rat Bcl-x(L) yielded two forms, one deamidated at -Asn-Gly-sequences to produce isoaspartates and the other not deamidated. The crystal structures of the two forms show that they both adopt an essentially identical backbone structure which resembles the fold of human Bcl-x(L): three layers of two alpha-helices each, capped at one end by two short helices. Both forms have a long disordered region, which contains the potential deamidation sites. The molecular structure exhibits a low level of interhelical interactions, the presence of three cavities, and a notable hydrophobic cleft surrounded by walls rich in basic residues. These unique structural features may be favorable for its accommodation into membranes or for possible rearrangement to modulate homo-/heterodimerization. Homology modeling of Bcl-2 and Bax, based on the Bcl-x(L), structure, suggests that Bax has the strongest potential for membrane insertion. Furthermore, we found a possible interface for interaction with non-Bcl-2 family member proteins, such as CED-4 homologues.