Cadherins form a large family of calcium-dependent adhesive proteins involved in morphogenesis, cell differentiation, and neuronal connectivity. Non-clustered δ1 protocadherins form a cadherin subgroup of proteins with seven extracellular cadherin (EC) repeats and cytoplasmic domains distinct from those of classical cadherins. Non-clustered δ1 protocadherins mediate homophilic adhesion and have been implicated in various diseases including asthma, autism, and cancer. Here we present X-ray crystal structures of human Protocadherin-1 (PCDH1), a δ1-protocadherin member essential for New World Hantavirus infection that is typically expressed in the brain, airway epithelium, skin keratinocytes, and lungs. The structures suggest a binding mode that involves antiparallel overlap of repeats EC1 to EC4. Mutagenesis combined with binding assays and biochemical experiments validated this mode of adhesion. Overall, these results reveal the molecular mechanism underlying adhesiveness of PCDH1 and δ1-protocadherins, also shedding light on PCDH1’s role in maintaining airway epithelial integrity, the loss of which causes respiratory diseases.

Organic materials generating pure white light emission have attracted considerable attention in recent times due to their potential applications in lighting and display devices. We have used anthracene carboxylic acid (AnA) and anthracene carbaldehyde (AnC) to generate white light using solvent induced selective self-assembly (SISSA). Mechanistically, SISSA prevents a fast intersystem crossing of the AnC monomer and generates an emissive state from the self-assembled AnC. While AnA emits in the blue region, the self-assembled AnC emits in the greenish yellow region with identical emission intensity. CIE coordinates (0.33, 0.33) of pure white light have been achieved by incorporating orange emitting rhodamine B. More importantly, the pure white light formation has been demonstrated at desired temperatures in both aqueous medium as well as in an agar-agar hydrogel.

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.

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150 WORDS) 1 Cadherins form a large family of calcium-dependent adhesive proteins involved in 2 morphogenesis, cell differentiation, and neuronal connectivity. Non-clustered δ1 protocadherins 3 form a cadherin subgroup of proteins with seven extracellular cadherin (EC) repeats and 4 cytoplasmic domains distinct from those of classical cadherins. The non-clustered δ1 5 protocadherins mediate homophilic adhesion and have been implicated in various diseases 6including asthma, autism, and cancer. Here we present X-ray crystal structures of Protocadherin-7 1 (PCDH1), a δ1-protocadherin member essential for New World hantavirus infection that is 8 typically expressed in the brain, airway epithelium, skin keratinocytes, and lungs. The structures 9 suggest a binding mode that involves antiparallel overlap of repeats EC1 to EC4. Mutagenesis 10 combined with binding assays and biochemical experiments validated this mode of adhesion. 11 Overall, these results reveal the molecular mechanism underlying adhesiveness of PCDH1 and 12 δ1-protocadherins, also shedding light on PCDH1's role in maintaining airway epithelial 13 integrity, the loss of which causes respiratory diseases. 14 15

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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 two non-classical 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.