3jz7
Crystal structure of the extracellular domains of coxsackie & adenovirus receptor from mouse (mCAR)
Structural highlights
FunctionCXAR_MOUSE Component of the epithelial apical junction complex that is essential for the tight junction integrity. Proposed to function as a homophilic cell adhesion molecule. Recruits MPDZ to intercellular contact sites. Probably involved in transepithelial migration of polymorphonuclear leukocytes (PMN) through adhesive interactions with AMICA1/JAML located in the plasma membrane of PMN (By similarity).[1] [2] [3] In vitro, acts as a receptor for group B coxsackieviruses and subgroup C of adenoviruses (AD2 and AD5).[4] [5] [6] 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 PubMedThe coxsackievirus-adenovirus receptor (CAR) is a member of the Ig superfamily strongly expressed in the developing nervous system. Our histological investigations during development reveal an initial uniform distribution of CAR on all neural cells with a concentration on membranes that face the margins of the nervous system (e.g., the basal laminae and the ventricular side). At more advanced stages, CAR becomes downregulated and restricted to specific regions including areas rich in axonal and dendritic surfaces. To study the function of CAR on neural cells, we used the fiber knob of the adenovirus, extracellular CAR domains, blocking antibodies to CAR, as well as CAR-deficient neural cells. Blocking antibodies were found to inhibit neurite extension in retina organ and retinal explant cultures, whereas the application of the recombinant fiber knob of the adenovirus subtype Ad2 or extracellular CAR domains promoted neurite extension and adhesion to extracellular matrices. We observed a promiscuous interaction of CAR with extracellular matrix glycoproteins, which was deduced from analytical ultracentrifugation experiments, affinity chromatography, and adhesion assays. The membrane proximal Ig domain of CAR, termed D2, was found to bind to a fibronectin fragment, including the heparin-binding domain 2, which promotes neurite extension of wild type, but not of CAR-deficient neural cells. In contrast to heterophilic interactions, homophilic association of CAR involves both Ig domains, as was revealed by ultracentrifugation, chemical cross-linking, and adhesion studies. The results of these functional and binding studies are correlated to a U-shaped homodimer of the complete extracellular domains of CAR detected by x-ray crystallography. The coxsackievirus-adenovirus receptor reveals complex homophilic and heterophilic interactions on neural cells.,Patzke C, Max KE, Behlke J, Schreiber J, Schmidt H, Dorner AA, Kroger S, Henning M, Otto A, Heinemann U, Rathjen FG J Neurosci. 2010 Feb 24;30(8):2897-910. PMID:20181587[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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