The Arabidopsis genes FT and TERMINAL FLOWER1 (TFL1) encode related proteins with similarity to human Raf kinase inhibitor protein. FT, and likely also TFL1, is recruited to the promoters of floral genes through interaction with FD, a bZIP transcription factor. FT, however, induces flowering, while TFL1 represses flowering. Residues responsible for the opposite activities of FT and TFL1 were mapped by examining plants that overexpress chimeric proteins. A region important in vivo localizes to a 14-amino-acid segment that evolves very rapidly in TFL1 orthologs, but is almost invariant in FT orthologs. Crystal structures show that this segment forms an external loop of variable conformation. The only residue unambiguously distinguishing the FT and TFL1 loops makes a hydrogen bond with a residue near the entrance of a potential ligand-binding pocket in TFL1, but not in FT. This pocket is contacted by a C-terminal peptide, which also contributes to the opposite FT and TFL1 activities. In combination, these results identify a molecular surface likely to be recognized by FT-and/or TFL1-specific interactors.

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The crystal structure of hPEBP suggests that the ligand-binding site could accommodate the phosphate head groups of membrane lipids, therefore allowing the protein to adhere to the inner leaf of bilipid membranes where it would be ideally positioned to relay signals from the membrane to the cytoplasm. The structure also suggests that ligand binding may lead to coordinated release of the N-terminal region of the protein to form the hippocampal neurostimulatory peptide, which is known to be active in the development of the hippocampus. These studies are consistent with a primary biological role for hPEBP as a transducer of signals from the interior membrane surface.

Tetraspanins are thought to facilitate the formation of multiprotein complexes at cell surfaces, but evidence illuminating the biologic importance of this role is sparse. Tetraspanin CD151 forms very stable laminin-binding complexes with integrins alpha3beta1 and alpha6beta1 in kidney and alpha3beta1 and alpha6beta4 in skin. It is encoded by a gene at the same position on chromosome 11p15.5 as the MER2 blood group gene. We show that CD151 expresses the MER2 blood group antigen and is located on erythrocytes. We examined CD151 in 3 MER2-negative patients (2 are sibs) of Indian Jewish origin with end-stage kidney disease. In addition to hereditary nephritis the sibs have sensorineural deafness, pretibial epidermolysis bullosa, and beta-thalassemia minor. The 3 patients are homozygous for a single nucleotide insertion (G383) in exon 5 of CD151, causing a frameshift and premature stop signal at codon 140. The resultant truncated protein would lack its integrin-binding domain. We conclude that CD151 is essential for the proper assembly of the glomerular and tubular basement membrane in kidney, has functional significance in the skin, is probably a component of the inner ear, and could play a role in erythropoiesis.