title: Occludin binds to the SH3-hinge-GuK unit of zonula occludens protein 1: potential mechanism of tight junction regulation.
abstract: The interaction between tight junction proteins occludin and zona occludens protein 1 (ZO-1) was clarified. The sequence cc1 within the hinge region of ZO-1, connecting its SH3 and GuK domains, was identified as a new association site for the occludin C-terminus, core binding area GLRSSKRNLRKSR (mouse ZO-1(606-618)). Occludin also bound to the sequence H2 within GuK, core area HKLRKNNH (ZO-1(759-766)). In occludin, the binding core was ELSRLDKELDDYREESEEY (mouse occludin(455-473)). Helicity of the sequences was suggested by circular dichroism. Because basic residues in ZO-1, acidic residues in occludin (underlined), coiled-coil helix-forming leucine heptad motifs (bold) in occludin and, probably, in cc1 were essential, we conclude that interactions were both helical and ionic. Moreover, the GuK domain bound other GuK molecules, suggesting oligomerization of ZO-1. Generally, the assumption is supported that the SH3-hinge-GuK region represents a functional and regulatory unit in ZO-1 forming a multiprotein tight junction complex with occludin.
authors.affiliation: Forschungsinstitut für Molekulare Pharmakologie, Robert-Rössle-Str. 10, 13125 Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schmidt
authors.forename: D I
authors.initials: DI
authors.lastname: Utepbergenov
authors.forename: S L
authors.initials: SL
authors.lastname: Mueller
authors.forename: M
authors.initials: M
authors.lastname: Beyermann
authors.forename: J
authors.initials: J
authors.lastname: Schneider-Mergener
authors.forename: G
authors.initials: G
authors.lastname: Krause
authors.forename: I E
authors.initials: IE
authors.lastname: Blasig
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019281:Dimerization; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D062793:Occludin; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D017433:Protein Structure, Secondary; D021122:Protein Subunits; D019108:Tight Junctions / Q000737:chemistry / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein; D018909:src Homology Domains
chemical_list: D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; C568986:Ocln protein, mouse; D010750:Phosphoproteins; D021122:Protein Subunits; C569042:TJP1 protein, human; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein