The energy landscape of modular repeat proteins: topology determines folding mechanism in the ankyrin family.
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.
Ferreiro
Diego U
DU
Center for Theoretical Biological Physics, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Cho
Samuel S
SS
Komives
Elizabeth A
EA
Wolynes
Peter G
PG
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
D017487:Ankyrins; D051880:Receptors, Notch; D051550:I-kappa B Kinase