title: Sequential protein unfolding through a carbon nanotube pore.
abstract: An assortment of biological processes, like protein degradation and the transport of proteins across membranes, depend on protein unfolding events mediated by nanopore interfaces. In this work, we exploit fully atomistic simulations of an artificial, CNT-based nanopore to investigate the nature of ubiquitin unfolding. With one end of the protein subjected to an external force, we observe non-canonical unfolding behaviour as ubiquitin is pulled through the pore opening. Secondary structural elements are sequentially detached from the protein and threaded into the nanotube, interestingly, the remaining part maintains native-like characteristics. The constraints of the nanopore interface thus facilitate the formation of stable "unfoldon" motifs above the nanotube aperture that can exist in the absence of specific native contacts with the other secondary structure. Destruction of these unfoldons gives rise to distinct force peaks in our simulations, providing us with a sensitive probe for studying the kinetics of serial unfolding events. Our detailed analysis of nanopore-mediated protein unfolding events not only provides insight into how related processes might proceed in the cell, but also serves to deepen our understanding of structural arrangements which form the basis for protein conformational stability.
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China. lijingyuan@ihep.ac.cn.
authors.forename: Zhonghe
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China. lijingyuan@ihep.ac.cn and Department of Physics, Zhejiang University, Hangzhou 310027, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: IBM Thomas J. Watson Research Center, Yorktown Heights, New York 10598, USA.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Weber
authors.affiliation: IBM Thomas J. Watson Research Center, Yorktown Heights, New York 10598, USA.
authors.forename: Binquan
authors.initials: B
authors.lastname: Luan
authors.affiliation: IBM Thomas J. Watson Research Center, Yorktown Heights, New York 10598, USA and Department of Chemistry, Columbia University, New York, New York 10027, USA.
authors.forename: Ruhong
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China. lijingyuan@ihep.ac.cn.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Li
mesh_terms: D008958:Models, Molecular; D058608:Nanopores; D037742:Nanotubes, Carbon; D011487:Protein Conformation; D017510:Protein Folding; D058767:Protein Unfolding; D011506:Proteins / Q000737:chemistry*
chemical_list: D037742:Nanotubes, Carbon; D011506:Proteins