Lesage F, Reyes R, Fink M, Duprat F, Guillemare E, Lazdunski M
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, 660, Valbonne, France.
EMBO J. 1996 Dec 2;15(23):6400-7.
TWIK-1 is a new type of K+ channel with two P domains and is abundantly expressed in human heart and brain. Here we show that TWIK-1 subunits can self-associate to give dimers containing an interchain disulfide bridge. This assembly involves a 34 amino acid domain that is localized to the extracellular M1P1 linker loop. Cysteine 69 which is part of this interacting domain is implicated in the formation of the disulfide bond. Replacing this cysteine with a serine residue results in the loss of functional K+ channel expression. This is the first example of a covalent association of functional subunits in voltage-sensitive channels via a disulfide bridge.
TWIK-1是一种新型的钾离子通道，具有两个P结构域，在人类心脏和大脑中大量表达。我们在此表明，TWIK-1亚基可以自我缔合形成含有链间二硫键的二聚体。这种组装涉及一个位于细胞外M1P1连接环的34个氨基酸的结构域。作为这个相互作用结构域一部分的半胱氨酸69参与了二硫键的形成。用丝氨酸残基取代这个半胱氨酸会导致功能性钾离子通道表达的丧失。这是电压敏感通道中功能性亚基通过二硫键进行共价缔合的首个例子。
