王昌河*, 谢振丽, 吕建伟, 于志丹, 邵淑丽*
本文旨在研究电压感受蛋白(voltage sensing proteins, VSPs)的保守基序、分析其序列特点并组建其电压感受模型。在UniProt数据库中的检索结果显示，现有的VSPs主要为电压门控型离子通道及电压依赖性磷酸激酶，其共同特点是均含有一个4次跨膜区，分别称为S1~S4 (Segment 1–4)。S1区主要负责其上膜与转运，S2~S4区是其感知膜电位变化的核心。profile-to-profile序列比对结果表明VSPs各跨膜区的保守基序非常相似，尤其是S4跨膜区均含基序[RK]-X(2)-R-X(2)-R-X(2)-[RK]，其特点是带正电荷的精氨酸残基(R)与两个疏水性或不带电荷的氨基酸残基交替排列，这是VSPs感知膜电位变化的核心区域。同时，四个跨膜区内均含大量具有较高α-螺旋结构形成倾向性的疏水性氨基酸残基，这可能是VSPs(尤其是带有大量正电荷的S4区域)能在胞膜上稳定存在的主要原因。此外，S3区内带负电荷的天冬氨酸残基(D)的保守性对VSPs感知膜电位变化具有重要意义，天冬氨酸残基与S4区的静电作用还可增加S4区在膜上的稳定性。
[Conserved motifs in voltage sensing proteins.] [Article in Chinese]
WANG Chang-He*, XIE Zhen-Li, LV Jian-Wei, YU Zhi-Dan, SHAO Shu-Li*
College of Life Science, Agriculture and Forestry, Qiqihar University, Qiqihar 161006, China
This paper was aimed to study conserved motifs of voltage sensing proteins (VSPs) and establish a voltage sensing model. All VSPs were collected from the Uniprot database using a comprehensive keyword search followed by manual curation, and the results indicated that there are only two types of known VSPs, voltage gated ion channels and voltage dependent phosphatases. All the VSPs have a common domain of four helical transmembrane segments (TMS, S1-S4), which constitute the voltage sensing module of the VSPs. The S1 segment was shown to be responsible for membrane targeting and insertion of these proteins, while S2-S4 segments, which can sense membrane potential, for protein properties. Conserved motifs/residues and their functional significance of each TMS were identified using profile-to-profile sequence alignments. Conserved motifs in these four segments are strikingly similar for all VSPs, especially, the conserved motif [RK]-X(2)-R-X(2)-R-X(2)-[RK] was presented in all the S4 segments, with positively charged arginine (R) alternating with two hydrophobic or uncharged residues. Movement of these arginines across the membrane electric field is the core mechanism by which the VSPs detect changes in membrane potential. The negatively charged aspartate (D) in the S3 segment is universally conserved in all the VSPs, suggesting that the aspartate residue may be involved in voltage sensing properties of VSPs as well as the electrostatic interactions with the positively charged residues in the S4 segment, which may enhance the thermodynamic stability of the S4 segments in plasma membrane.
通讯作者：王昌河,邵淑丽 E-mail: firstname.lastname@example.org,email@example.com
王昌河, 谢振丽, 吕建伟, 于志丹, 邵淑丽. 电压感受蛋白的保守基序及其序列分析[J]. 生理学报 2012; 64 (4): 379-386.
WANG Chang-He, XIE Zhen-Li, LV Jian-Wei, YU Zhi-Dan, SHAO Shu-Li. [Conserved motifs in voltage sensing proteins.] [Article in Chinese]. Acta Physiol Sin 2012; 64 (4): 379-386 (in Chinese with English abstract).