Structural highlights
Disease
[CRUM1_HUMAN] Pigmented paravenous retinochoroidal atrophy;Leber congenital amaurosis;Retinitis pigmentosa. CRB1 mutations have been found in various retinal dystrophies, chronic and disabling disorders of visual function. They predominantly involve the posterior portion of the ocular fundus, due to degeneration in the sensory layer of the retina, retinal pigment epithelium, Bruch membrane, choroid, or a combination of these tissues. Onset of inherited retinal dystrophies is painless, bilateral and typically progressive. Most people experience gradual peripheral vision loss or tunnel vision, and difficulties with poor illumination and night vision. Central vision is usually unaffected, so the person may still be able to read. However, it can also deteriorate to cause total blindness. Examples of retinal dystrophies are retinitis pigmentosa, Leber congenital amaurosis, cone-rod dystrophy among others. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
Function
[MPP5_HUMAN] May play a role in tight junctions biogenesis and in the establishment of cell polarity in epithelial cells. May modulate SC6A1/GAT1-mediated GABA uptake by stabilizing the transporter. Required for localization of EZR to the apical membrane of parietal cells and may play a role in the dynamic remodeling of the apical cytoskeleton (By similarity). [CRUM1_HUMAN] Plays a role in photoreceptor morphogenesis in the retina. May maintain cell polarization and adhesion.
Publication Abstract from PubMed
Many components of epithelial polarity protein complexes possess PDZ domains that are required for protein interaction and recruitment to the apical plasma membrane. Apical localization of the Crumbs (Crb) transmembrane protein requires a PDZ-mediated interaction with Pals1 (protein-associated with Lin7, Stardust, MPP5), a member of the p55 family of membrane-associated guanylate kinases (MAGUKs). This study describes the molecular interaction between the Crb carboxy-terminal motif (ERLI), which is required for Drosophila cell polarity, and the Pals1 PDZ domain using crystallography and fluorescence polarization. Only the last four Crb residues contribute to Pals1 PDZ-domain binding affinity, with specificity contributed by conserved charged interactions. Comparison of the Crb-bound Pals1 PDZ structure with an apo Pals1 structure reveals a key Phe side chain that gates access to the PDZ peptide-binding groove. Removal of this side chain enhances the binding affinity by more than fivefold, suggesting that access of Crb to Pals1 may be regulated by intradomain contacts or by protein-protein interaction.
Structures of the human Pals1 PDZ domain with and without ligand suggest gated access of Crb to the PDZ peptide-binding groove.,Ivanova ME, Fletcher GC, O'Reilly N, Purkiss AG, Thompson BJ, McDonald NQ Acta Crystallogr D Biol Crystallogr. 2015 Mar 1;71(Pt 3):555-64. doi:, 10.1107/S139900471402776X. Epub 2015 Feb 26. PMID:25760605[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ivanova ME, Fletcher GC, O'Reilly N, Purkiss AG, Thompson BJ, McDonald NQ. Structures of the human Pals1 PDZ domain with and without ligand suggest gated access of Crb to the PDZ peptide-binding groove. Acta Crystallogr D Biol Crystallogr. 2015 Mar 1;71(Pt 3):555-64. doi:, 10.1107/S139900471402776X. Epub 2015 Feb 26. PMID:25760605 doi:http://dx.doi.org/10.1107/S139900471402776X
