title: The energy landscape of modular repeat proteins: topology determines folding mechanism in the ankyrin family.
abstract: Proteins consisting of repeating amino acid motifs are abundant in all kingdoms of life, especially in higher eukaryotes. Repeat-containing proteins self-organize into elongated non-globular structures. Do the same general underlying principles that dictate the folding of globular domains apply also to these extended topologies? Using a simplified structure-based model capturing a perfectly funneled energy landscape, we surveyed the predicted mechanism of folding for ankyrin repeat containing proteins. The ankyrin family is one of the most extensively studied classes of non-globular folds. The model based only on native contacts reproduces most of the experimental observations on the folding of these proteins, including a folding mechanism that is reminiscent of a nucleation propagation growth. The confluence of simulation and experimental results suggests that the folding of non-globular proteins is accurately described by a funneled energy landscape, in which topology plays a determinant role in the folding mechanism.
authors.affiliation: Center for Theoretical Biological Physics, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Diego U
authors.initials: DU
authors.lastname: Ferreiro
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Cho
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Komives
authors.forename: Peter G
authors.initials: PG
authors.lastname: Wolynes
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D017487:Ankyrins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D003198:Computer Simulation; D051550:I-kappa B Kinase / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D017510:Protein Folding; D051880:Receptors, Notch / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D017487:Ankyrins; D051880:Receptors, Notch; D051550:I-kappa B Kinase