A highly compliant protein native state with a spontaneous-like mechanical unfolding pathway

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  • Petur O. Heidarsson
  • ,
  • Immanuel Valpapuram
  • ,
  • Carlo Camilloni
  • ,
  • Alberto Imparato
  • Guido Tiana
  • ,
  • Flemming M. Poulsen
  • ,
  • Birthe B. Kragelund
  • ,
  • Ciro Cecconi
The mechanical properties of proteins and their force-induced
structural changes play key roles in many biological processes. Previous studies
have shown that natively folded proteins are brittle under tension, unfolding after
small mechanical deformations, while partially folded intermediate states, such as
molten globules, are compliant and can deform elastically a great amount before
crossing the transition state barrier. Moreover, under tension proteins appear to
unfold through a different sequence of events than during spontaneous unfolding.
Here, we describe the response to force of the four-α-helix acyl-CoA binding
protein (ACBP) in the low-force regime using optical tweezers and ratcheted
molecular dynamics simulations. The results of our studies reveal an
unprecedented mechanical behavior of a natively folded protein. ACBP displays an atypical compliance along two nearly
orthogonal pulling axes, with transition states located almost halfway between the unfolded and folded states. Surprisingly, the
deformability of ACBP is greater than that observed for the highly pliant molten globule intermediate states. Furthermore, when
manipulated from the N- and C-termini, ACBP unfolds by populating a transition state that resembles that observed during
chemical denaturation, both for structure and position along the reaction coordinate. Our data provide the first experimental
evidence of a spontaneous-like mechanical unfolding pathway of a protein. The mechanical behavior of ACBP is discussed in
terms of topology and helix propensity.
Original languageEnglish
JournalJournal of American Chemical Society
Pages (from-to)17068-17075
Number of pages8
Publication statusPublished - 2012

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