| First Author | Tsunenari T | Year | 2003 |
| Journal | J Biol Chem | Volume | 278 |
| Issue | 42 | Pages | 41114-25 |
| PubMed ID | 12907679 | Mgi Jnum | J:84780 |
| Mgi Id | MGI:2670184 | Doi | 10.1074/jbc.M306150200 |
| Citation | Tsunenari T, et al. (2003) Structure-function analysis of the bestrophin family of anion channels. J Biol Chem 278(42):41114-25 |
| abstractText | The bestrophins are a newly described family of anion channels unrelated in primary sequence to any previously characterized channel proteins. The human genome codes for four bestrophins, each of which confers a distinctive plasma membrane conductance on transfected 293 cells. Extracellular treatment with methanethiosulfonate ethyltrimethylammonium (MTSET) of a series of substitution mutants that eliminate one or more cysteines from human bestrophin1 demonstrates that cysteine 69 is the single endogenous cysteine responsible for MTSET inhibition of whole-cell current. Cysteines introduced between positions 78-99 and 223-226 are also accessible to external MTSET, with MTSET modification at positions 79, 80, 83, and 90 producing a 2-6-fold increase in whole-cell current. The latter set of four cysteine-substitution mutants define a region that appears to mediate allosteric control of channel activity. Mapping of transmembrane topography by insertion of N-linked glycosylation sites and tobacco etch virus protease cleavage sites provides evidence for cytosolic N and C termini and an unexpected transmembrane topography with at least three extracellular loops that include positions 60-63, 212-227, and 261-267. These experiments provide the first structural analysis of the bestrophin channel family. |
