title: The molten globule state is unusually deformable under mechanical force.
abstract: Recently, the role of force in cellular processes has become more evident, and now with advances in force spectroscopy, the response of proteins to force can be directly studied. Such studies have found that native proteins are brittle, and thus not very deformable. Here, we examine the mechanical properties of a class of intermediates referred to as the molten globule state. Using optical trap force spectroscopy, we investigated the response to force of the native and molten globule states of apomyoglobin along different pulling axes. Unlike natively folded proteins, the molten globule state of apomyoglobin is compliant (large distance to the transition state); this large compliance means that the molten globule is more deformable and the unfolding rate is more sensitive to force (the application of force or tension will have a more dramatic effect on the unfolding rate). Our studies suggest that these are general properties of molten globules and could have important implications for mechanical processes in the cell.
authors.affiliation: Biophysics Graduate Group, California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA 94720-3220, USA.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Elms
authors.forename: John D
authors.initials: JD
authors.lastname: Chodera
authors.forename: Carlos
authors.initials: C
authors.lastname: Bustamante
authors.forename: Susan
authors.initials: S
authors.lastname: Marqusee
mesh_terms: D000465:Algorithms; D001059:Apoproteins / Q000737:chemistry*; D001499:Bayes Theorem; D001671:Biochemistry / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D008390:Markov Chains; D018625:Microscopy, Atomic Force / Q000379:methods; D009154:Mutation; D009211:Myoglobin / Q000737:chemistry*; D052898:Optical Tweezers; D010957:Plasmids / Q000378:metabolism; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013314:Stress, Mechanical
chemical_list: D001059:Apoproteins; D009211:Myoglobin; C010857:apomyoglobin