5iu9
From Proteopedia
Crystal Structure of Zebrafish Protocadherin-19 EC1-4
Structural highlights
FunctionPCD19_DANRE Calcium-dependent cell-adhesion protein (PubMed:21115806). Essential for the early stages of neurulation in the anterior neural plate (PubMed:19615992). Shows little cell adhesion activity on its own but exhibits robust homophilic cell adhesion when in a complex with cadherin cdh2 and appears to mediate the adhesion while cdh2 acts as a cell adhesion cofactor in the complex (PubMed:21115806, PubMed:22184198, PubMed:33004519). Functions with cdh2 to coordinate cell adhesion and cell movements during neurulation (PubMed:21115806). Contributes to neural progenitor cell patterning with cdh2 by promoting homophilic cell interactions (PubMed:33004519). Regulates the columnar organization of neurons in the optic tectum (PubMed:26598617).[1] [2] [3] [4] [5] Publication Abstract from PubMedNon-clustered delta-protocadherins are homophilic cell adhesion molecules essential for the development of the vertebrate nervous system, as several are closely linked to neurodevelopmental disorders. Mutations in protocadherin-19 (PCDH19) result in a female-limited, infant-onset form of epilepsy (PCDH19-FE). Over 100 mutations in PCDH19 have been identified in patients with PCDH19-FE, about half of which are missense mutations in the adhesive extracellular domain. Neither the mechanism of homophilic adhesion by PCDH19, nor the biochemical effects of missense mutations are understood. Here we present a crystallographic structure of the minimal adhesive fragment of the zebrafish Pcdh19 extracellular domain. This structure reveals the adhesive interface for Pcdh19, which is broadly relevant to both non-clustered delta and clustered protocadherin subfamilies. In addition, we show that several PCDH19-FE missense mutations localize to the adhesive interface and abolish Pcdh19 adhesion in in vitro assays, thus revealing the biochemical basis of their pathogenic effects during brain development. Structural determinants of adhesion by Protocadherin-19 and implications for its role in epilepsy.,Cooper SR, Jontes JD, Sotomayor M Elife. 2016 Oct 26;5. doi: 10.7554/eLife.18529. PMID:27787195[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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