Crystal Structure of PK10, Unique Characteristics of a MAPK Fromleishmania Major
Acta crystallographica Section A, Foundations of crystallography/Acta crystallographica Section A(2011)
摘要
The bullous pemphigoid autoantigen 1 (BPAG1) is a member of the plakin family of cytolinker proteins that associate with and crosslink components of the various cytoskeletal systems [1].The epithelial isoform of BPAG1, known as BPAG1e or BP230, is a component of hemidesmosomes (HDs) that are multiprotein complexes that mediate firm adhesion of epithelial cells to the underlying basement membrane [2].In the HDs, BP230 links the integrin α6β4 (a laminin receptor) to the cytokeratin system.BP230 contains in its N-terminal region a plakin domain (a sequence of ~ 1000 residues conserved in the plakin family) formed by eight Spectrin Repeats (SR2 to SR9) and a SH3 domain inserted in the SR5.Upstream of the SR2 there is a 55-residues long isoform-specific tail.The N-terminal region of BP230 harbors binding site for the cytoplasmic region of the integrin β4 subunit [3].Here we report the crystal structure of the SR2 of BP230.The structure was solved by molecular replacement and was refined against data to 2.0 Å resolution.The structure shows the characteristic SR fold, which consists of three α-helices connected by short loops.The helices are organized in a bundle with a left-handed twist that is stabilized by coiled coil interactions.The SR2 of BP230 shares a 31% sequence identity with the equivalent region of plectin, which is another member of the plakin family present in HDs.Most of the conserved residues are located in the core of the helical bundle; thus, the polypeptide backbones of the SR2 of BP230 and plectin are almost identical.Nonetheless, there are significant differences in the solvent accessible surfaces between BP230 and plectin.Finally, we have used circular dichroism and limited proteolysis to analyze the structure of the Nterminal tail of BP230.Our data suggest that the N-terminal tail is an intrinsically disordered region.
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关键词
Ser/Thr protein kinases (STPKs)
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