title: The morphology of decorated amyloid fibers is controlled by the conformation and position of the displayed protein.
abstract: Self-assembled structures capable of mediating electron transfer are an attractive scientific and technological goal. Therefore, systematic variants of SH3-Cytochrome b(562) fusion proteins were designed to make amyloid fibers displaying heme-b(562) electron transfer complexes. TEM and AFM data show that fiber morphology responds systematically to placement of b(562) within the fusion proteins. UV-vis spectroscopy shows that, for the fusion proteins under test, only half the fiber-borne b(562) binds heme with high affinity. Cofactor binding also improves the AFM imaging properties and changes the fiber morphology through changes in cytochrome conformation. Systematic observations and measurements of fiber geometry suggest that longitudinal registry of subfilaments within the fiber, mediated by the interaction and conformation of the displayed proteins and their interaction with surfaces, gives rise to the observed morphologies, including defects and kinks. Of most interest is the role of small molecule modulation of fiber structure and mechanical stability. A minimum complexity model is proposed to capture and explain the fiber morphology in the light of these results. Understanding the complex interplay between these factors will enable a fiber design that supports longitudinal electron transfer.
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, U.K.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Forman
authors.forename: Adrian A
authors.initials: AA
authors.lastname: Nickson
authors.forename: Spencer J
authors.initials: SJ
authors.lastname: Anthony-Cahill
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Baldwin
authors.forename: Gillian
authors.initials: G
authors.lastname: Kaggwa
authors.forename: Urs
authors.initials: U
authors.lastname: Feber
authors.forename: Khizar
authors.initials: K
authors.lastname: Sheikh
authors.forename: Suzanne P
authors.initials: SP
authors.lastname: Jarvis
authors.forename: Paul D
authors.initials: PD
authors.lastname: Barker
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D003573:Cytochrome b Group / Q000737:chemistry / Q000378:metabolism; D004579:Electron Transport; D006418:Heme / Q000378:metabolism; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D055503:Protein Multimerization; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D018909:src Homology Domains
chemical_list: D000682:Amyloid; D003573:Cytochrome b Group; D011993:Recombinant Fusion Proteins; D006418:Heme