Complex interactions at the helix-helix interface stabilize the glycophorin A transmembrane dimer
Complex interactions at the helix-helix interface stabilize the glycophorin A transmembrane dimer
复制标题
DOI：
10.1016/j.jmb.2004.09.011
复制
发表时间：
2004-11-05
影响因子：
5.6
通讯作者：
Fleming, KG
中科院分区：
文献类型：
--
作者：
Doura, AK;Fleming, KG
为了探索血型糖蛋白A二聚化基序中的残基相互作用，进行了螺旋-螺旋界面处的丙氨酸扫描双突变体分析。这些数据揭示了叠加效应和耦合效应的结合。大多数的双突变体被发现是相同的或稍微更稳定的比将由单点突变体的能量成本的总和预测。突变位点的邻近性与这些位点之间偶联的存在无关。先前的研究表明，血型糖蛋白A单体的一个面含有一个特定的含甘氨酸基序（GxxxG），被认为是跨膜螺旋缔合的驱动力。双突变周期表明，GxxxG基序的螺旋-螺旋界面的其余部分的关系是复杂的。含有消除GxxxG基序的突变的序列保留二聚化的能力，而含有GxxxG基序的序列似乎不能形成二聚体。弱耦合和添加剂双突变体的能量效应可以解释的变化，在二聚体界面的货车范德华相互作用。这些结果强调了这样一个事实，即二聚体界面的序列背景调节血型糖蛋白A GxxxG介导的跨膜二聚化反应的强度。(C)2004爱思唯尔有限公司保留所有权利。
To explore the residue interactions in the glycophorin A dimerization motif, an alanine scan double mutant analysis at the helix-helix interface was carried out. These data reveal a combination of additive and coupled effects. The majority of the double mutants are found to be equally or slightly more stable than would be predicted by the sum of the energetic cost of the single-point mutants. The proximity of the mutated sites is not related to the presence of coupling between those sites. Previous studies reveal that a single face of the glycophorin A monomer contains a specific glycine-containing motif (GxxxG) that is thought to be a driving force for the association of transmembrane helices. Double mutant cycles suggest that the relationship of the GxxxG motif to the remainder of the helix-helix interface is complex. Sequences containing mutations that abolish the GxxxG motif retain an ability to dimerize, while a sequence containing a GxxxG motif appears unable to form dimers. The energetic effects of weakly coupled and additive double mutants can be explained by changes in van der Waals interactions at the dimer interface. These results emphasize the fact that the sequence context of the dimer interface modulates the strength of the glycophorin A GxxxG-mediated transmembrane dimerization reaction. (C) 2004 Elsevier Ltd. All rights reserved.