Molecular Packing and Packing Defects in Helical Membrane Proteins
Peter Werner Hildebrand 1*, Kristian Rother 1, Andrean Goede 1, Robert Preissner 1 and Cornelius Frömmel 1
1 University Medicine Berlin
* To whom correspondence should be addressed. E-mail: peter.hildebrand{at}charite.de.
Submitted on July 13, 2004
Revised on August 31, 2004
Accepted on 1 November 2004
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Abstract |
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The packing of helices spanning lipid bilayers is crucial for the stability and function of alpha-helical membrane proteins. Using a modified Voronoi procedure, we calculated packing densities for helix-helix contacts in membrane spanning domains. Our results show that the transmembrane helices of protein channels and transporters are significantly more loosely packed compared with helices in globular proteins. The observed packing deficiencies of these membrane proteins are also reflected by a higher amount of cavities at functionally important sites. The cavities positioned along the gated pores of membrane channels and transporters are noticeably lined by polar amino acids that should be exposed to the aqueous medium when the protein is in the open state. In contrast non-polar amino acids surround the cavities in those protein regions, where large rearrangements are supposed to take place, as near the hinge regions of transporters, or at restriction sites of protein channels. We presume that the observed deficiencies of helix-helix packing are essential for the helical mobility that sustains the function of many membrane protein channels and transporters.
Key Words:
channel, packing density, protein function, protein mobility, transmembrane, transporter
