Protein domain
Protein domain
The LU domain (Ly-6 antigen /uPAR ) is an evolutionarily conserved protein domain of the three-finger protein superfamily. This domain is found in the extracellular domains of cell-surface receptors and in either GPI-anchored or secreted globular proteins , for example the Ly-6 family, CD59 , and Sgp-2.[ 2] [ 3]
A variety of GPI-linked cell-surface glycoproteins are composed of one or more copies of a conserved LU domain of about 100 amino-acid residues.[ 4] [ 5] uPAR has three tandem LU domains.[ 3]
Structure
This domain folds into five antiparallel beta sheets , a structure common to the three-finger protein family . The domain typically contains ten well-conserved cysteine residues involved in five disulfide bonds , though some examples such as two of the three uPAR domains have fewer.[ 3]
Examples
Besides uPAR, other receptors with LU domains include members of the transforming growth factor beta receptor (TGF-beta) superfamily, such as the activin type 2 receptor ;[ 6] bone morphogenetic protein receptor, type IA .[ 7] CD59 antigen , LYNX1 , SLURP1 , and SLURP2 .[ 2] [ 8]
Subfamilies
Human proteins containing this domain
ARS; CD177 ; CD59 ; LY6D ; LY6E ; LY6H ; LYNX1 ;
LYPD2 ; LYPD3 ; LYPD4 ; LYPD5 ; LYPD6 ; PLAUR ; PSCA ;
SLURP2 ; SLURP1 ; SPACA4 ; TEX101 ;
Functions
Many LU domain containing proteins are involved in cholinergic signaling and bind acetylcholine receptors, notably linking their function to a common mechanism of 3FTx toxicity.[ 2] [ 3] [ 9] three-finger toxin (3FTx).[ 10] CD59 antigen , have well-studied functions in regulation of the immune system .[ 9]
References
^ PDB : 2J8B Leath KJ, Johnson S, Roversi P, Hughes TR, Smith RA, Mackenzie L, Morgan BP, Lea SM (August 2007). "High-resolution structures of bacterially expressed soluble human CD59" . Acta Crystallographica. Section F, Structural Biology and Crystallization Communications . 63 (Pt 8): 648– 52. doi :10.1107/S1744309107033477 . PMC 2335151 PMID 17671359 . ^ a b c Kessler P, Marchot P, Silva M, Servent D (August 2017). "The three-finger toxin fold: a multifunctional structural scaffold able to modulate cholinergic functions" . Journal of Neurochemistry . 142 (Suppl 2): 7– 18. doi :10.1111/jnc.13975 PMID 28326549 . ^ a b c d Loughner CL, Bruford EA, McAndrews MS, Delp EE, Swamynathan S, Swamynathan SK (April 2016). "Organization, evolution and functions of the human and mouse Ly6/uPAR family genes" . Human Genomics . 10 : 10. doi :10.1186/s40246-016-0074-2 PMC 4839075 PMID 27098205 . ^ Behrendt N, Ploug M, Patthy L, Houen G, Blasi F, Danø K (April 1991). "The ligand-binding domain of the cell surface receptor for urokinase-type plasminogen activator" . The Journal of Biological Chemistry . 266 (12): 7842– 7. doi :10.1016/S0021-9258(20)89526-X PMID 1850423 . ^ Ploug M, Kjalke M, Rønne E, Weidle U, Høyer-Hansen G, Danø K (August 1993). "Localization of the disulfide bonds in the NH2-terminal domain of the cellular receptor for human urokinase-type plasminogen activator. A domain structure belonging to a novel superfamily of glycolipid-anchored membrane proteins" . The Journal of Biological Chemistry . 268 (23): 17539– 46. doi :10.1016/S0021-9258(19)85366-8 PMID 8394346 . ^ Greenwald J, Fischer WH, Vale WW, Choe S (January 1999). "Three-finger toxin fold for the extracellular ligand-binding domain of the type II activin receptor serine kinase". Nature Structural Biology . 6 (1): 18– 22. doi :10.1038/4887 . PMID 9886286 . S2CID 26301441 . ^ Kirsch T, Sebald W, Dreyer MK (June 2000). "Crystal structure of the BMP-2-BRIA ectodomain complex". Nature Structural Biology . 7 (6): 492– 6. doi :10.1038/75903 . PMID 10881198 . S2CID 19403233 . ^ Galat A (November 2008). "The three-fingered protein domain of the human genome" . Cellular and Molecular Life Sciences . 65 (21): 3481– 93. doi :10.1007/s00018-008-8473-8 . PMC 11131612 PMID 18821057 . S2CID 19931506 . ^ a b Tsetlin VI (February 2015). "Three-finger snake neurotoxins and Ly6 proteins targeting nicotinic acetylcholine receptors: pharmacological tools and endogenous modulators". Trends in Pharmacological Sciences . 36 (2): 109– 23. doi :10.1016/j.tips.2014.11.003 . PMID 25528970 . ^ Fry BG (March 2005). "From genome to "venome": molecular origin and evolution of the snake venom proteome inferred from phylogenetic analysis of toxin sequences and related body proteins" . Genome Research . 15 (3): 403– 20. doi :10.1101/gr.3228405 . PMC 551567 PMID 15741511 .
