6j69
From Proteopedia
Structure of KIBRA and Dendrin Complex
Structural highlights
Function[KIBRA_MOUSE] Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with NF2 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. Acts as a transcriptional coactivator of ESR1 which plays an essential role in DYNLL1-mediated ESR1 transactivation. Regulates collagen-stimulated activation of the ERK/MAPK cascade. Modulates directional migration of podocytes. Acts as a substrate for PRKCZ and may be associated with memory performance (By similarity). Regulates collagen-stimulated activation of the ERK/MAPK cascade.[1] [DEND_MOUSE] Promotes apoptosis of kidney glomerular podocytes. Podocytes are highly specialized cells essential to the ultrafiltration of blood, resulting in the extraction of urine and the retention of protein.[2] Publication Abstract from PubMedKibra is a synaptic scaffold protein regulating learning and memory. Alterations of Kibra-encoding gene WWC1 cause various neuronal disorders, including Alzheimer's disease and Tourette syndrome. However, the molecular mechanism underlying Kibra's function in neurons is poorly understood. Here we discover that Kibra, via its N-terminal WW12 tandem domains, binds to a postsynaptic density enriched protein, Dendrin, with a nanomolar dissociation constant. On the basis of the structure of Kibra WW12 in complex with Dendrin PY motifs, we developed a potent peptide inhibitor capable of specifically blocking the binding between Kibra and Dendrin in neurons. Systematic administration of the inhibitory peptide attenuated excitatory synaptic transmission, completely blocked long-term potentiation induction, and impaired spatial learning and memory. A Kibra mutation found in Tourette syndrome patients causes defects in binding to Dendrin. Thus, Kibra can modulate spatial learning and memory via binding to Dendrin. Kibra Modulates Learning and Memory via Binding to Dendrin.,Ji Z, Li H, Yang Z, Huang X, Ke X, Ma S, Lin Z, Lu Y, Zhang M Cell Rep. 2019 Feb 19;26(8):2064-2077.e7. doi: 10.1016/j.celrep.2019.01.097. PMID:30784589[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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