Structural determinants of transmembrane helical proteins.
We identify a structural feature of transmembrane helical proteins that restricts their conformational space and suggests a new way of understanding the construction and stability of their native states. We show that five kinds of well-known specific favorable interhelical interactions (hydrogen bonds, aromatic interactions, salt bridges, and two interactions from packing motifs) precisely determine the packing of the transmembrane helices in 15 diverse proteins. To show this, we iteratively reassemble the helix bundle of each protein using only these interactions, generic interaction geometries, and individual helix backbone conformations. On average, the representative set of rebuilt structures best satisfying the constraints imposed by the five types of interhelical interactions has an average Calpha root-mean-square deviation from the native of 1.03 A. Implications for protein folding, structure and motion prediction, modeling, and design are discussed.
Harrington
Susan E
SE
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel.
Ben-Tal
Nir
N
D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008565:Membrane Proteins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D008565:Membrane Proteins