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-a-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.

A Highly Compliant Protein Native State with a Spontaneous-like Mechanical Unfolding Pathway / Heidarsson, Petur O.; Samidass, VALPAPURAM IMMANUEL; Camilloni, Carlo; Imparato, Alberto; Tiana, Guido; Poulsen, Flemming M.; Kragelund, Birthe B.; Cecconi, Ciro. - In: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. - ISSN 0002-7863. - 134:41(2012), pp. 17068-17075. [10.1021/ja305862m]

A Highly Compliant Protein Native State with a Spontaneous-like Mechanical Unfolding Pathway

SAMIDASS, VALPAPURAM IMMANUEL;CECCONI, CIRO
2012

Abstract

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-a-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.
2012
134
41
17068
17075
A Highly Compliant Protein Native State with a Spontaneous-like Mechanical Unfolding Pathway / Heidarsson, Petur O.; Samidass, VALPAPURAM IMMANUEL; Camilloni, Carlo; Imparato, Alberto; Tiana, Guido; Poulsen, Flemming M.; Kragelund, Birthe B.; Cecconi, Ciro. - In: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. - ISSN 0002-7863. - 134:41(2012), pp. 17068-17075. [10.1021/ja305862m]
Heidarsson, Petur O.; Samidass, VALPAPURAM IMMANUEL; Camilloni, Carlo; Imparato, Alberto; Tiana, Guido; Poulsen, Flemming M.; Kragelund, Birthe B.; Cecconi, Ciro
File in questo prodotto:
File Dimensione Formato  
Heidarsson-JACS-acbp_compliant_native_state.pdf

Accesso riservato

Descrizione: Articolo
Tipologia: Versione pubblicata dall'editore
Dimensione 1.34 MB
Formato Adobe PDF
1.34 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1070003
Citazioni
  • ???jsp.display-item.citation.pmc??? 12
  • Scopus 26
  • ???jsp.display-item.citation.isi??? 25
social impact