CLC家族的渠道和运输因子是同型二聚体，但供在渠道和离子耦合腔（它们在运输因子中协调Cl- 和 H+的反向转运）中阴离子扩散的水孔却是完全包含在这些同型二聚体的每个亚单元内，说明这些复合物起“并行通道”的作用。这种观点在一项实验中得到证实：在该实验中，突变被用来使来自大肠杆菌的一个ClC Cl-/H+“交换器”的二聚体界面失去稳定性。这样得到的渠道是一个单聚体，然而它在功能上却几乎跟野生型渠道完全相同。这意味着，跨亚单位的相互作用并不是CLC运输因子中的Cl-/H+交换所必需的，这便提出一个问题：野生型运输因子为什么是同型二聚体？（生物谷Bioon.com）
生物谷推荐原文出处：
Nature doi:10.1038/nature09556
Design, function and structure of a monomeric ClC transporter
Janice L. Robertson,Ludmila Kolmakova-Partensky& Christopher Miller
Channels and transporters of the ClC family cause the transmembrane movement of inorganic anions in service of a variety of biological tasks, from the unusual—the generation of the kilowatt pulses with which electric fish stun their prey—to the quotidian—the acidification of endosomes, vacuoles and lysosomes1. The homodimeric architecture of ClC proteins, initially inferred from single-molecule studies of an elasmobranch Cl? channel2 and later confirmed by crystal structures of bacterial Cl?/H+ antiporters3, 4, is apparently universal. Moreover, the basic machinery that enables ion movement through these proteins—the aqueous pores for anion diffusion in the channels and the ion-coupling chambers that coordinate Cl? and H+ antiport in the transporters—are contained wholly within each subunit of the homodimer. The near-normal function of a bacterial ClC transporter straitjacketed by covalent crosslinks across the dimer interface and the behaviour of a concatemeric human homologue argue that the transport cycle resides within each subunit and does not require rigid-body rearrangements between subunits5, 6. However, this evidence is only inferential, and because examples are known in which quaternary rearrangements of extramembrane ClC domains that contribute to dimerization modulate transport activity7, we cannot declare as definitive a ‘parallel-pathways’ picture in which the homodimer consists of two single-subunit transporters operating independently. A strong prediction of such a view is that it should in principle be possible to obtain a monomeric ClC. Here we exploit the known structure of a ClC Cl?/H+ exchanger, ClC-ec1 from Escherichia coli, to design mutants that destabilize the dimer interface while preserving both the structure and the transport function of individual subunits. The results demonstrate that the ClC subunit alone is the basic functional unit for transport and that cross-subunit interaction is not required for Cl?/H+ exchange in ClC transporters.
