Structural highlights
Disease
[OCLN_HUMAN] Defects in OCLN are the cause of band-like calcification with simplified gyration and polymicrogyria (BLCPMG) [MIM:251290]; also known as pseudo-TORCH syndrome. BLCPMG is a neurologic disorder with characteristic clinical and neuroradiologic features that mimic intrauterine TORCH infection in the absence of evidence of infection. Affected individuals have congenital microcephaly, intracranial calcifications, and severe developmental delay.[1]
Function
[OCLN_HUMAN] May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions.[2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ O'Driscoll MC, Daly SB, Urquhart JE, Black GC, Pilz DT, Brockmann K, McEntagart M, Abdel-Salam G, Zaki M, Wolf NI, Ladda RL, Sell S, D'Arrigo S, Squier W, Dobyns WB, Livingston JH, Crow YJ. Recessive mutations in the gene encoding the tight junction protein occludin cause band-like calcification with simplified gyration and polymicrogyria. Am J Hum Genet. 2010 Sep 10;87(3):354-64. doi: 10.1016/j.ajhg.2010.07.012. Epub, 2010 Aug 19. PMID:20727516 doi:10.1016/j.ajhg.2010.07.012
- ↑ Suzuki T, Elias BC, Seth A, Shen L, Turner JR, Giorgianni F, Desiderio D, Guntaka R, Rao R. PKC eta regulates occludin phosphorylation and epithelial tight junction integrity. Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):61-6. doi: 10.1073/pnas.0802741106., Epub 2008 Dec 29. PMID:19114660 doi:10.1073/pnas.0802741106
- ↑ Li Y, Fanning AS, Anderson JM, Lavie A. Structure of the conserved cytoplasmic C-terminal domain of occludin: identification of the ZO-1 binding surface. J Mol Biol. 2005 Sep 9;352(1):151-64. PMID:16081103 doi:10.1016/j.jmb.2005.07.017
