1xaw
From Proteopedia
|
crystal structure of the cytoplasmic distal C-terminal domain of occludin
Overview
Occludin is a transmembrane protein localized at tight junctions whose, functions are complex yet poorly understood. Current evidence supports a, role for occludin in both the formation of the paracellular barrier and in, cell signaling. While the N-terminal extracellular domains of occludin, mediate homotypic adhesion, the distal C-terminal cytoplasmic domain of, occludin controls protein targeting and endocytosis. The C terminus can, also bind to the scaffolding proteins ZO-1, ZO-2, ZO-3, cingulin, the, membrane trafficking protein VAP33, and the cytoskeletal protein F-actin, suggesting an important role for this domain. This domain is highly, homologous to an important functional domain in the C terminus of the ELL, family of RNA polymerase II transcription factors. To explore the function, of occludin, we determined the high-resolution crystal structure of its, C-terminal distal cytoplasmic domain. The structure comprises three, helices that form two separate anti-parallel coiled-coils and a loop that, packs tightly against one of the coiled-coils. Using in vitro binding, studies and site-directed mutagenesis, we have identified a large, positively charged surface that contains the binding site for ZO-1, and, this surface is required for proper localization of occludin to cell-cell, junctions. On the basis of sequence conservation, we predict that occludin, domains from different species and the C-terminal domain of the ELL, transcription factors share a very similar structure. Our results provide, a model to further test the function of occludin and its binding to other, proteins.
About this Structure
1XAW is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of the conserved cytoplasmic C-terminal domain of occludin: identification of the ZO-1 binding surface., Li Y, Fanning AS, Anderson JM, Lavie A, J Mol Biol. 2005 Sep 9;352(1):151-64. PMID:16081103
Page seeded by OCA on Mon Nov 12 20:02:54 2007
