5cmn
From Proteopedia
FLRT3 LRR domain in complex with LPHN3 Olfactomedin domain
Structural highlights
Disease[FLRT3_HUMAN] Kallmann syndrome. The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. Some patients carrying mutations in FLRT3 also have a mutation in another HH-associated gene including FGFR1, HS6ST1 and FGF17 (PubMed:23643382).[1] Function[FLRT3_HUMAN] May have a function in cell adhesion and/or receptor signaling. [LPHN3_HUMAN] May be involved in the development of glutamatergic synapses in the cortex. Important in determining the connectivity rates between the principal neurons in the cortex (By similarity). Publication Abstract from PubMedFibronectin leucine-rich repeat transmembrane proteins (FLRTs) are cell-adhesion molecules with emerging functions in cortical development and synapse formation. Their extracellular regions interact with latrophilins (LPHNs) to mediate synapse development, and with Uncoordinated-5 (UNC5)/netrin receptors to control the migration of neurons in the developing cortex. Here, we present the crystal structures of FLRT3 in isolation and in complex with LPHN3. The LPHN3/FLRT3 structure reveals that LPHN3 binds to FLRT3 at a site distinct from UNC5. Structure-based mutations specifically disrupt LPHN3/FLRT3 binding, but do not disturb their interactions with other proteins or their cell-membrane localization. Thus, they can be used as molecular tools to dissect the functions of FLRTs and LPHNs in vivo. Our results suggest that UNC5 and LPHN3 can simultaneously bind to FLRT3, forming a trimeric complex, and that FLRT3 may form transsynaptic complexes with both LPHN3 and UNC5. These findings provide molecular insights for understanding the role of cell-adhesion proteins in synapse function. Structural Basis of Latrophilin-FLRT-UNC5 Interaction in Cell Adhesion.,Lu YC, Nazarko OV, Sando R 3rd, Salzman GS, Sudhof TC, Arac D Structure. 2015 Jul 28. pii: S0969-2126(15)00277-4. doi:, 10.1016/j.str.2015.06.024. PMID:26235030[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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