title: Size-dependent impact of CNTs on dynamic properties of calmodulin.
abstract: There are growing concerns about the biosafety of nanomaterials such as carbon nanotubes (CNTs) as their applications become more widespread. We report here a theoretical and experimental study of the binding of various sizes of CNTs [CNT (4,4), (5,5), (6,6) and (7,7)] to calmodulin (CaM) protein and, in particular, their impact on the Ca(2+)-dependent dynamic properties of CaM. Our simulations show that all the CNTs can plug into the hydrophobic binding pocket of Ca(2+)-bound CaM with binding affinities comparable with the native substrate M13 peptide. Even though CNT (4,4) shows a similar behavior to the M13 peptide in its dissociation from Ca(2+)-free CaM, wider CNTs still bind firmly to CaM, indicating a potential failure of Ca(2+) regulation. Such a size-dependent impact of CNTs on the dynamic properties of CaM is a result of the excessively strong hydrophobic interactions between the wider CNTs and CaM. These simulation results were confirmed by circular dichroism spectroscopy, which showed that the secondary structures of CaM become insensitive to Ca(2+) concentrations after the addition of CNTs. Our findings indicate that the cytotoxicity of nanoparticles to proteins arises not only from the inhibition of static protein structures (binding pockets), but also from impacts on their dynamic properties.
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, China. lijingyuan@ihep.ac.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.forename: Liming
authors.initials: L
authors.lastname: Wang
authors.forename: Seung-gu
authors.initials: SG
authors.lastname: Kang
authors.forename: Lina
authors.initials: L
authors.lastname: Zhao
authors.forename: Mingjuan
authors.initials: M
authors.lastname: Ji
authors.forename: Chunying
authors.initials: C
authors.lastname: Chen
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Ruhong
authors.initials: R
authors.lastname: Zhou
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Li
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry; D002147:Calmodulin / Q000737:chemistry*; D002942:Circular Dichroism; D003198:Computer Simulation; D057927:Hydrophobic and Hydrophilic Interactions; D007477:Ions; D008024:Ligands; D056004:Molecular Dynamics Simulation; D036103:Nanotechnology / Q000379:methods*; D037742:Nanotubes, Carbon / Q000737:chemistry*; D010316:Particle Size; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary
chemical_list: D002147:Calmodulin; D007477:Ions; D008024:Ligands; D037742:Nanotubes, Carbon; D010455:Peptides; D002118:Calcium