7n86

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Crystal Structure of Human Protocadherin-24 EC1-2 Form II

Structural highlights

7n86 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.175Å
Ligands:	, , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CDHR2_HUMAN Intermicrovillar adhesion molecule that forms, via its extracellular domain, calcium-dependent heterophilic complexes with CDHR5 on adjacent microvilli. Thereby, controls the packing of microvilli at the apical membrane of epithelial cells. Through its cytoplasmic domain, interacts with microvillus cytoplasmic proteins to form the intermicrovillar adhesion complex/IMAC. This complex plays a central role in microvilli and epithelial brush border differentiation (PubMed:24725409). May also play a role in cell-cell adhesion and contact inhibition in epithelial cells (PubMed:12117771).^[1] ^[2]

Publication Abstract from PubMed

Enterocytes are specialized epithelial cells lining the luminal surface of the small intestine that build densely packed arrays of microvilli known as brush borders. These microvilli drive nutrient absorption and are arranged in a hexagonal pattern maintained by intermicrovillar links formed by 2 nonclassical members of the cadherin superfamily of calcium-dependent cell adhesion proteins: protocadherin-24 (PCDH24, also known as CDHR2) and the mucin-like protocadherin (CDHR5). The extracellular domains of these proteins are involved in heterophilic and homophilic interactions important for intermicrovillar function, yet the structural determinants of these interactions remain unresolved. Here, we present X-ray crystal structures of the PCDH24 and CDHR5 extracellular tips and analyze their species-specific features relevant for adhesive interactions. In parallel, we use binding assays to identify the PCDH24 and CDHR5 domains involved in both heterophilic and homophilic adhesion for human and mouse proteins. Our results suggest that homophilic and heterophilic interactions involving PCDH24 and CDHR5 are species dependent with unique and distinct minimal adhesive units.

Heterophilic and homophilic cadherin interactions in intestinal intermicrovillar links are species dependent.,Gray ME, Johnson ZR, Modak D, Tamilselvan E, Tyska MJ, Sotomayor M PLoS Biol. 2021 Dec 6;19(12):e3001463. doi: 10.1371/journal.pbio.3001463., eCollection 2021 Dec. PMID:34871294^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Okazaki N, Takahashi N, Kojima S, Masuho Y, Koga H. Protocadherin LKC, a new candidate for a tumor suppressor of colon and liver cancers, its association with contact inhibition of cell proliferation. Carcinogenesis. 2002 Jul;23(7):1139-48. PMID:12117771
↑ Crawley SW, Shifrin DA Jr, Grega-Larson NE, McConnell RE, Benesh AE, Mao S, Zheng Y, Zheng QY, Nam KT, Millis BA, Kachar B, Tyska MJ. Intestinal brush border assembly driven by protocadherin-based intermicrovillar adhesion. Cell. 2014 Apr 10;157(2):433-46. doi: 10.1016/j.cell.2014.01.067. PMID:24725409 doi:http://dx.doi.org/10.1016/j.cell.2014.01.067
↑ Gray ME, Johnson ZR, Modak D, Tamilselvan E, Tyska MJ, Sotomayor M. Heterophilic and homophilic cadherin interactions in intestinal intermicrovillar links are species dependent. PLoS Biol. 2021 Dec 6;19(12):e3001463. PMID:34871294 doi:10.1371/journal.pbio.3001463