Construction of helix-bundle membrane proteins

• Published in: Advances in Protein Chemistry Vol. 63; pp. 19 - 46
• Main Authors: Chamberlain, Aaron K, Faham, Salem, Yohannan, Sarah, Bowie, James U
• Format: Book Chapter Journal Article
• Language: English
• Published: United States Elsevier Science & Technology 2003
• Subjects: Animal physiology; Biochemistry; Biophysical Phenomena; Biophysics; Cell Membrane - chemistry; Cell Membrane - metabolism; Hydrogen Bonding; Lipid Metabolism; Models, Biological; Protein Structure, Secondary; Proteins - chemistry; Thermodynamics
• ISBN: 9780120342631; 0120342634
• ISSN: 0065-3233; 1557-8941
• DOI: 10.1016/S0065-3233(03)63002-0

This chapter presents some of the current understanding of the structure of α-helical membrane proteins and the forces that stabilize their structures. It focuses on the folding and stability of membrane proteins within the bilayer rather than on the thermodyamics of helix insertion into the membrane. It is not possible to point to a force that dominates in the construction of helix bundle membrane proteins. Hydrogen bonds can be extremely strong, but are relatively sparse and are not critical for the development of stable helix-helix interactions. Van der Waals interactions are certainly important, but the fact that a well-packed leucine zipper interface is not sufficient to drive TM helix association suggests that packing alone is not enough. Although the complex interplay between lipid structure and protein structure must play an important role, the fact that many membrane proteins remain folded and functional in detergent micelles suggests that lipid structure alone cannot entirely explain membrane protein architecture.