1WPA: 1.5 Angstrom Crystal Structure Of Human Occludin Fragment 413-522

Citation:
Abstract
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.
PDB ID: 1WPADownload
MMDB ID: 34579
PDB Deposition Date: 2004/9/1
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 1.5  Å
Source Organism:
Similar Structures:
Biological Unit for 1WPA: monomeric; determined by author
Molecular Components in 1WPA
Label Count Molecule
Protein (1 molecule)
1
Occludin(Gene symbol: OCLN)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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