title: Single-molecule observation of helix staggering, sliding, and coiled coil misfolding.
abstract: The biological functions of coiled coils generally depend on efficient folding and perfect pairing of their α-helices. Dynamic changes in the helical registry that lead to staggered helices have only been proposed for a few special systems and not found in generic coiled coils. Here, we report our observations of multiple staggered helical structures of two canonical coiled coils. The partially folded structures are formed predominantly by coiled coil misfolding and occasionally by helix sliding. Using high-resolution optical tweezers, we characterized their energies and transition kinetics at a single-molecule level. The staggered states occur less than 2% of the time and about 0.1% of the time at zero force. We conclude that dynamic changes in helical registry may be a general property of coiled coils. Our findings should have broad and unique implications in functions and dysfunctions of proteins containing coiled coils.
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Zhiqun
authors.initials: Z
authors.lastname: Xi
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.forename: George
authors.initials: G
authors.lastname: Sirinakis
authors.forename: Honglian
authors.initials: H
authors.lastname: Guo
authors.forename: Yongli
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D004247:DNA / Q000378:metabolism; D007700:Kinetics; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D017510:Protein Folding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D011506:Proteins; D004247:DNA