walsh-completestructure-2015.pdf (7.49 MB)
Complete structure of an epithelial keratin dimer: Implications for intermediate filament assembly
journal contribution
posted on 2015-07-16, 00:00 authored by D J Bray, Tiffany WalshTiffany Walsh, M G Noro, R NotmanKeratins are cytoskeletal proteins that hierarchically arrange into filaments, starting with the dimer sub-unit. They are integral to the structural support of cells, in skin, hair and nails. In skin, keratin is thought to play a critical role in conferring the barrier properties and elasticity of skin. In general, the keratin dimer is broadly described by a tri-domain structure: a head, a central rod and a tail. As yet, no atomistic-scale picture of the entire dimer structure exists; this information is pivotal for establishing molecular-level connections between structure and function in intermediate filament proteins. The roles of the head and tail domains in facilitating keratin filament assembly and function remain as open questions. To address these, we report results of molecular dynamics simulations of the entire epithelial human K1/K10 keratin dimer. Our findings comprise: (1) the first three-dimensional structural models of the complete dimer unit, comprising of the head, rod and tail domains; (2) new insights into the chirality of the rod-domain twist gained from analysis of the full domain structure; (3) evidence for tri-subdomain partitioning in the head and tail domains; and, (4) identification of the residue characteristics that mediate non-covalent contact between the chains in the dimer. Our findings are immediately applicable to other epithelial keratins, such as K8/K18 and K5/K14, and to intermediate filament proteins in general. Copyright:
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Journal
PLoS ONEVolume
10Issue
7Publisher DOI
eISSN
1932-6203Publication classification
C Journal article; C1 Refereed article in a scholarly journalCopyright notice
2015, The AuthorsUsage metrics
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Science & TechnologyMultidisciplinary SciencesScience & Technology - Other TopicsMOLECULAR-DYNAMICSMECHANICAL-PROPERTIESCOILED-COILTAIL DOMAINVIMENTINORGANIZATIONPROTEINSKERATODERMASEGMENTSMUTATIONAmino Acid SequenceDisulfidesHumansHydrogen BondingIntermediate FilamentsKeratin-1Keratin-10Molecular Dynamics SimulationMolecular Sequence DataProtein FoldingProtein MultimerizationProtein Structure, SecondaryProtein Structure, TertiarySequence Alignment
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