TITLE

K+ channels lacking the 'tetramerization' domain: implications for pore structure

AUTHOR(S)
Kobertz, William R.; Miller, Christopher
PUB. DATE
December 1999
SOURCE
Nature Structural Biology;Dec99, Vol. 6 Issue 12, p1122
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
The difficulty of obtaining high-resolution structures of integral membrane proteins has been a frustrating barrier to understanding the membrane-based functions of living cells. The mere handful of such structures stands out in dismal contrast to the cornucopia of water-soluble proteins comprehensible at the atomic level. Nevertheless, crystallographically tractable preparations of aqueous domains of membrane proteins have provided molecular insight into phenomena as varied as chemotaxis, immune cell responses to antigens, viral infectivity and cellular synthesis of ATP. Recently, the first structural glimpse of a neuronal ion channel was reported ? the T1, or 'tetramerization,' domain of a Shaker-type voltage-gated K+ channel at 1.6 Ã… resolution. The isolated domain associates into a water-soluble four-fold symmetric homotetramer. This structure prompted the novel, provocative proposal that the T1 domain is an essential component of the ion permeation pathway, forming a previously unsuspected ion-coordinating constriction on the cytoplasmic side of the channel and acting as the receptor for the pore-blocking 'ball and chain' inactivation peptide. It has also been commonly conjectured that the T1 domain is required for tetramerization in the channel maturation process. By studying the detailed properties of Shaker K+ channels in which the T1 domain is deleted, we show all these proposals to be invalid. The structure of the T1 domain expressed in isolation is therefore unlikely to mirror in detail its structure when attached to the ion-conducting channel.
ACCESSION #
8816736

 

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