Pathways and intermediates in forced unfolding of spectrin repeats.
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.
Altmann
Stephan M
SM
European Molecular Biology Laboratory, Cell Biology and Biophysics Program, Meyerhofstr. 1, 69117 Heidelberg, Germany.
Grünberg
Raik G
RG
Lenne
Pierre-François
PF
Ylänne
Jari
J
Raae
Arnt
A
Herbert
Kristina
K
Saraste
Matti
M
Nilges
Michael
M
Hörber
J K Heinrich
JK
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
D013049:Spectrin