6e2j
From Proteopedia
Crystal structure of the heterocomplex between human keratin 1 coil 1B containing S233L mutation and wild-type human keratin 10 coil 1B
Structural highlights
Disease[K2C1_HUMAN] Epidermolytic palmoplantar keratoderma;Ichthyosis hystrix of Curth-Macklin;Annular epidermolytic ichthyosis;Epidermolytic ichthyosis;Keratosis palmoplantaris striata. 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. 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. [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. Function[K2C1_HUMAN] May regulate the activity of kinases such as PKC and SRC via binding to integrin beta-1 (ITB1) and the receptor of activated protein C kinase 1 (RACK1). In complex with C1QBP is a high affinity receptor for kininogen-1/HMWK.[1] [2] Publication Abstract from PubMedTo 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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