1WPA

1.5 Angstrom crystal structure of human occludin fragment 413-522

Summary for 1WPA

• Entry DOI: 10.2210/pdb1wpa/pdb
• Descriptor: Occludin (2 entities in total)
• Functional Keywords: occludin, coiled-coil, zo-1 binding, transmembrane protein, cell adhesion
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Multi-pass membrane protein: Q16625
• Total number of polymer chains: 1
• Total formula weight: 13695.21

Authors

Li, Y.,Lavie, A.,Fanning, A.S.,Anderson, J.M. (deposition date: 2004-09-01, release date: 2005-09-06, Last modification date: 2024-03-13)

Primary citation

Li, Y.,Fanning, A.S.,Anderson, J.M.,Lavie, A.
Structure of the conserved cytoplasmic C-terminal domain of occludin: identification of the ZO-1 binding surface.
J.Mol.Biol., 352:151-164, 2005

PubMed 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.

PubMed: 16081103
DOI: 10.1016/j.jmb.2005.07.017

Experimental method

X-RAY DIFFRACTION (1.5 Å)