title: Pathways and intermediates in forced unfolding of spectrin repeats.
abstract: Spectrin repeats are triple-helical coiled-coil domains found in many proteins that are regularly subjected to mechanical stress. We used atomic force microscopy technique and steered molecular dynamics simulations to study the behavior of a wild-type spectrin repeat and two mutants. The experiments indicate that spectrin repeats can form stable unfolding intermediates when subjected to external forces. In the simulations the unfolding proceeded via a variety of pathways. Stable intermediates were associated to kinking of the central helix close to a proline residue. A mutant stabilizing the central helix showed no intermediates in experiments, in agreement with simulation. Spectrin repeats may thus function as elastic elements, extendable to intermediate states at various lengths.
authors.affiliation: European Molecular Biology Laboratory, Cell Biology and Biophysics Program, Meyerhofstr. 1, 69117 Heidelberg, Germany.
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Altmann
authors.forename: Raik G
authors.initials: RG
authors.lastname: Grünberg
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Lenne
authors.forename: Jari
authors.initials: J
authors.lastname: Ylänne
authors.forename: Arnt
authors.initials: A
authors.lastname: Raae
authors.forename: Kristina
authors.initials: K
authors.lastname: Herbert
authors.forename: Matti
authors.initials: M
authors.lastname: Saraste
authors.forename: Michael
authors.initials: M
authors.lastname: Nilges
authors.forename: J K Heinrich
authors.initials: JK
authors.lastname: Hörber
mesh_terms: D000818:Animals; D002645:Chickens; D002942:Circular Dichroism; D003198:Computer Simulation; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011487:Protein Conformation; D017510:Protein Folding; D013049:Spectrin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D013049:Spectrin