Evolution and Medical Significance of LU Domain−Containing Proteins

International Journal of Molecular Sciences

StephenG. Young¹  JulieMaja Leth²  KatrineZinck Leth-Espensen²  Anne-Marie Lund Winther²  Anni Kumari²  KristianKølby Kristensen²  Michael Ploug² 

[1] Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA;Finsen Laboratory, Ole Maaloes Vej 5, Righospitalet,DK-2200 Copenhagen, Denmark;

关键词: uPAR;    snake venom α-neurotoxins;    GPIHBP1;    plesiotypic disulfide bonds;    protein evolution;    Ly6/uPAR domains;    protein module;    protein domain;   

DOI  :  10.3390/ijms20112760

来源: DOAJ

【 摘 要 】

Proteins containing Ly6/uPAR (LU) domains exhibit very diverse biological functions and have broad taxonomic distributions in eukaryotes. In general, they adopt a characteristic three-fingered folding topology with three long loops projecting from a disulfide-rich globular core. The majority of the members of this protein domain family contain only a single LU domain, which can be secreted, glycolipid anchored, or constitute the extracellular ligand binding domain of type-I membrane proteins. Nonetheless, a few proteins contain multiple LU domains, for example, the urokinase receptor uPAR, C4.4A, and Haldisin. In the current review, we will discuss evolutionary aspects of this protein domain family with special emphasis on variations in their consensus disulfide bond patterns. Furthermore, we will present selected cases where missense mutations in LU domain−containing proteins leads to dysfunctional proteins that are causally linked to genesis of human disease.

【 授权许可】

Unknown