6ec0

Crystal structure of the wild-type heterocomplex between coil 1B domains of human intermediate filament proteins keratin 1 (KRT1) and keratin 10 (KRT10)Crystal structure of the wild-type heterocomplex between coil 1B domains of human intermediate filament proteins keratin 1 (KRT1) and keratin 10 (KRT10)

Structural highlights 6ec0 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , Related: 6e2j Gene: KRT1 (HUMAN), KRT10, KPP (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [K1C10_HUMAN] Congenital reticular ichthyosiform erythroderma;Annular epidermolytic ichthyosis;Epidermolytic ichthyosis. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Publication Abstract from PubMed To characterize keratin intermediate filament assembly mechanisms at atomic resolution, we determined the crystal structure of wild-type human keratin-1/keratin-10 helix 1B heterotetramer at 3.0 A resolution. It revealed biochemical determinants for the A11 mode of axial alignment in keratin filaments. Four regions on a hydrophobic face of the K1/K10-1B heterodimer dictated tetramer assembly: the N-terminal hydrophobic pocket (defined by L227(K1), Y230(K1), F231(K1), and F234(K1)), the K10 hydrophobic stripe, K1 interaction residues, and the C-terminal anchoring knob (formed by F314(K1) and L318(K1)). Mutation of both knob residues to alanine disrupted keratin 1B tetramer and full-length filament assembly. Individual knob residue mutant F314A(K1), but not L318A(K1), abolished 1B tetramer formation. The K1-1B knob/pocket mechanism is conserved across keratins and many non-keratin intermediate filaments. To demonstrate how pathogenic mutations cause skin disease by altering filament assembly, we additionally determined the 2.39 A structure of K1/10-1B containing a S233L(K1) mutation linked to epidermolytic palmoplantar keratoderma. Light scattering and circular dichroism measurements demonstrated enhanced aggregation of K1(S233L)/K10-1B in solution without affecting secondary structure. The K1(S233L)/K10-1B octamer structure revealed S233L(K1) causes aberrant hydrophobic interactions between 1B tetramers. Human keratin 1/10-1B tetramer structures reveal a knob-pocket mechanism in intermediate filament assembly.,Eldirany SA, Ho M, Hinbest AJ, Lomakin IB, Bunick CG EMBO J. 2019 Apr 29. pii: embj.2018100741. doi: 10.15252/embj.2018100741. PMID:31036554 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Keratins

spinqualitylabelsall models 6ec0, resolution 2.98Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image