title: The self-assembly of a mini-fibril with axial periodicity from a designed collagen-mimetic triple helix.
abstract: In this work we describe the self-assembly of a collagen-like periodic mini-fibril from a recombinant triple helix. The triple helix, designated Col108, is expressed in Escherichia coli using an artificial gene and consists of a 378-residue triple helix domain organized into three pseudo-repeating sequence units. The peptide forms a stable triple helix with a melting temperature of 41 °C. Upon increases of pH and temperature, Col108 self-assembles in solution into smooth mini-fibrils with the cross-striated banding pattern typical of fibrillar collagens. The banding pattern is characterized by an axially repeating feature of ∼35 nm as observed by transmission electron microscopy and atomic force microscopy. Both the negatively stained and the positively stained transmission electron microscopy patterns of the Col108 mini-fibrils are consistent with a staggered arrangement of triple helices having a staggering value of 123 residues, a value closely connected to the size of one repeat sequence unit. A mechanism is proposed for the mini-fibril formation of Col108 in which the axial periodicity is instigated by the built-in sequence periodicity and stabilized by the optimized interactions between the triple helices in a 1-unit staggered arrangement. Lacking hydroxyproline residues and telopeptides, two factors implicated in the fibrillogenesis of native collagen, the Col108 mini-fibrils demonstrate that sequence features of the triple helical domain alone are sufficient to "code" for axially repeating periodicity of fibrils. To our knowledge, Col108 is the first designed triple helix to self-assemble into periodic fibrils and offers a unique opportunity to unravel the specific molecular interactions of collagen fibrillogenesis.
authors: From the Department of Chemistry, Hunter College of City University of New York, New York, New York 10065.
authors: Parminder Jeet
authors: PJ
authors: Kaur
authors: From the Department of Chemistry, Hunter College of City University of New York, New York, New York 10065.
authors: Rebecca
authors: R
authors: Strawn
authors: From the Department of Chemistry, Hunter College of City University of New York, New York, New York 10065.
authors: Hanying
authors: H
authors: Bai
authors: From the Department of Chemistry, Hunter College of City University of New York, New York, New York 10065.
authors: Ke
authors: K
authors: Xu
authors: From the Department of Chemistry, Hunter College of City University of New York, New York, New York 10065.
authors: Gabriel
authors: G
authors: Ordas
authors: From the Department of Chemistry, Hunter College of City University of New York, New York, New York 10065.
authors: Hiroshi
authors: H
authors: Matsui
authors: From the Department of Chemistry, Hunter College of City University of New York, New York, New York 10065 Yujia.xu@hunter.cuny.edu.
authors: Yujia
authors: Y
authors: Xu
mesh_terms: D000595:Amino Acid Sequence; D003094:Collagen / Q000737:chemistry* / Q000648:ultrastructure; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D011487:Protein Conformation
chemical_list: D003094:Collagen
keywords: Collagen Triple Helix; D-Periodic Fibril; Fibril Formation; Peptide Interaction; Protein Aggregation; Protein Assembly; Protein Complex; Protein Design