Home

About

Advanced Search

Browse by Discipline

Scientific Societies

E-print Alerts

Add E-prints

E-print Network
FAQHELPSITE MAPCONTACT US


  Advanced Search  

 
Channel-Lining Residues in the M3 Membrane-Spanning Segment of the Cystic Fibrosis Transmembrane Conductance Regulator
 

Summary: Channel-Lining Residues in the M3 Membrane-Spanning Segment of the Cystic
Fibrosis Transmembrane Conductance Regulator
Myles H. Akabas*
Center for Molecular Recognition and Departments of Physiology & Cellular Biophysics and Medicine,
College of Physicians and Surgeons, Columbia UniVersity, 630 West 168th Street, New York, New York 10032
ReceiVed April 29, 1998; ReVised Manuscript ReceiVed June 26, 1998
ABSTRACT: The cystic fibrosis transmembrane conductance regulator (CFTR) forms a chloride-selective
channel. Residues from the 12 putative membrane-spanning segments form at least part of the channel
lining. We need to identify the channel-lining residues in order to understand the structural basis for the
channel's functional properties. Using the substituted-cysteine-accessibility method we mutated to cysteine,
one at a time, 24 consecutive residues (Asp192-Ile215) in the M3 membrane-spanning segment. Cysteines
substituted for His199, Phe200, Trp202, Ile203, Pro205, Gln207, Leu211, and Leu214 reacted with charged,
sulfhydryl-specific reagents that are derivatives of methanethiosulfonate (MTS). We infer that these residues
are on the water-accessible surface of the protein and probably form a portion of the channel lining.
When plotted on an R-helical wheel the exposed residues from Gln207 to Leu214 lie within an arc of
60; the exposed residues in the cytoplasmic half (His199-Ile203) lie within an arc of 160. We infer
that the secondary structures of the extracellular and cytoplasmic halves of M3 are R-helical and that
Pro205, in the middle of the M3 segment, may bend the M3 segment, moving the cytoplasmic end of the
segment in toward the central axis of the channel. The bend in the M3 segment may help to narrow the
channel lumen near the cytoplasmic end. In addition, unlike full-length CFTR, the current induced by

  

Source: Akabas, Myles - Department of Physiology and Biophysics, Albert Einstein College of Medicine, Yeshiva University

 

Collections: Biology and Medicine