title: Protein Motifs. 7. The four-helix bundle: what determines a fold?
abstract: The four-helix bundle motif occurs in many structural contexts and in proteins that are functionally diverse. The motif can be classified into individual folds on the basis of topological and geometric properties. It has been thoroughly investigated structurally by both nuclear magnetic resonance and x-ray crystallography. Many mutants of four-helix bundles have been generated, and the motif has also been the target of de novo design studies. Taken together, these studies provide an opportunity to examine many of the forces governing protein folding. In this article we consider the relative importance of the burial of hydrophobic residues, loss of conformational entropy, packing interactions, interhelical turn composition, and helical dipole interactions all within the context of a single folding motif. We conclude by examining why de novo designed four-helix bundle proteins possess flexible interiors, and possible mechanisms by which natural proteins may lock their cores into rigid structures.
authors.affiliation: Department of Chemistry, Princeton University, New Jersey 08544-1009, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kamtekar
authors.forename: M H
authors.initials: MH
authors.lastname: Hecht
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry; D003573:Cytochrome b Group / Q000737:chemistry; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D005656:Fungal Proteins / Q000737:chemistry; D008958:Models, Molecular; D009038:Motion; D017510:Protein Folding; D011494:Protein Kinases / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry; D029701:Saccharomyces cerevisiae Proteins; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D003573:Cytochrome b Group; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D005656:Fungal Proteins; D016601:RNA-Binding Proteins; C054243:Rop protein, ColE1 plasmid; D029701:Saccharomyces cerevisiae Proteins; C017850:cytochrome b562, E coli; D011494:Protein Kinases