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32nd Annual North American Cystic Fibrosis Conference

W23--CFTR: Structure Function & Dynamics of CFTR Ion Channel

Oct 20, 2018 10:30am ‐ Oct 20, 2018 11:50am


Description

CFTR is a chloride channel related to the multi-domain ATP binding cassette (ABC) transporter family. Mutations compromising CFTR folding, such as the prevalent F508del, result in faulty maturation, poor localization to the cell surface, and reduced channel function. Mutations that alter the energetic equilibria and native state conformational dynamics of CFTR likely result in changes to channel gating and conductance. The first cryo-electron microscopy structures of CFTR provide snapshots of the protein in multiple conformational states. However, understanding channel gating and its regulation by both ATP binding and phosphorylation requires in-depth understanding of the dynamics and conformational plasticity of the protein. An integrated structural and functional model of CFTR gating will facilitate understanding of the impact of clinical mutations and the ways that small molecules may provide correction and potentiation.

Learning Objectives:

  • Evaluate the existing structures of CFTR and identify regions of CFTR critical for proper channel biosynthesis and function.
  • Identify conformational and dynamic processes that are critical to CFTR channel gating.
  • Describe structural and conformational states that facilitate CFTR correction and potentiation by small molecules.

Workshop Chair(s):

Workshop Speaker(s):

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