Interactions between the transmembrane helices of the cystic fibrosis transmembrane conductance regulator (CFTR).
Published: 2004
Language: eng
Number of pages: 106
Description: Many membrane-based mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) involve introduction of a polar residue, which can lock helices together via a side chain-side chain interhelical non-native hydrogen bond to a neighboring wild type polar residue [i.e., Val 232-to-Asp (TM4) to Gln207 (TM3) (Therien, Grant & Deber, Nat. Struct. Biol., 2001]. We studied the Gln 207 H-bond 'capture potential' by performing an Asp 'walk' through TM4 in a series of TM3/4 helix-loop-helix (hairpin) constructs, assessing factors including the Asp position relative to the helix-helix interface, and side chain length and polarity. Diagnostic gel shift assays on SDS-PAGE were used to measure 'open-closed' states of each hairpin. In related experiments, L346P and R347P mutants were investigated in a TM5/6 hairpin to determine why R347P inserts properly in the membrane, while L346P does not. The overall results help explain the molecular basis for aberrant CFTR function in CF-phenotypic TM domain mutants.
Notes: Adviser:  Charles M. Deber.

Thesis (M.Sc.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Masters Abstracts International, Volume: 42-06, page: 2205.

MICR copy on microfiche (2 microfiches).