Plant PR-5 proteins as mammalian therapeutic agents

Abstract

Proteins of the PR-5 family having a lectin-like β barrel domain control apoptosis in yeast through receptor binding. Receptors that specifically bind to PR-5 proteins having a lectin-like β barrel domain have been found to be homologous to mammalian adiponectin receptors, and such PR-5 proteins can act as functional homologues of adiponectin and control adiponectin response in mammals. PR-5 proteins having a lectin-like β barrel domain, for example osmotin, can be used in the treatment of conditions in mammals which are the result of activation or inhibition of adiponectin receptor-mediated metaboloic pathways. PR-5 proteins having a lectin-like β barrel domain, nucleic acids encoding such proteins, and receptors that specifically bind such proteins, can also be used in screening and rational design of new therapeutic agents for use in mammals.

1 . A pharmaceutical composition comprising a PR-5 protein having a lectin-like β barrel domain.  
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the PR-5 protein is osmotin [SEQ ID NO. 3], or a homolog thereof having a lectin-like β barrel domain.  
     
     
         3 . A method for treating a mammal suffering from a disorder that is the result of activation or inhibition of a metabolic pathway mediated by adiponectin or an adiponectin-like protein, comprising administration of a PR-5 protein having a lectin-like β barrel domain.  
     
     
         4 . The method of  claim 3 , wherein the disorder is selected from the group consisting of type II diabetes, insulin resistance, hyperlipidemia, arteriosclerosis, and heart disease.  
     
     
         5 . The method of  claim 4 , wherein the disorder is type II diabetes.  
     
     
         6 . The method of  claim 4 , wherein the disorder is insulin resistance.  
     
     
         7 . The method of  claim 4 , wherein the disorder is hyperlipidemia.  
     
     
         8 . The method of  claim 4 , wherein the disorder is arteriosclerosis.  
     
     
         9 . The method of  claim 4 , wherein the disorder is heart disease.  
     
     
         10 . The method of  claim 3 , wherein the PR-5 protein is osmotin [SEQ ID NO. 3], or a homolog of osmotin having a lectin-like β barrel domain.  
     
     
         11 . The method of  claim 4 , wherein the PR-5 protein is osmotin [SEQ ID NO. 3], or a homologue of osmotin having a lectin-like β barrel domain.  
     
     
         12 . Use of a PR-5 protein in the rational design of a therapeutic agent that is an agonist or an antagonist of all or part of the adiponectin targets in a mammalian cell.  
     
     
         13 . The use according to  claim 12 , wherein the therapeutic agent is an agonist.  
     
     
         14 . The use according to  claim 12 , wherein the therapeutic agent is an antagonist.  
     
     
         15 . The use according to  claim 12 , wherein the PR-5 protein is osmotin [SEQ ID NO: 3].  
     
     
         16 . The use according to  claim 12 , wherein the rational design includes structure/function analysis.  
     
     
         17 . Use of a nucleic acid sequence that encodes a PR-5 protein having a lectin-like β barrel domain in the rational design of a therapeutic agent that is an agonist or antagonist of all or part of the adiponectin targets in a mammalian cell.  
     
     
         18 . The use according to  claim 17 , wherein the therapeutic agent is an agonist.  
     
     
         19 . The use according to  claim 17 , wherein the therapeutic agent is an antagonist.  
     
     
         20 . The use according to  claim 17 , wherein the nucleic acid sequence is SEQ ID NO. 1.  
     
     
         21 . The use according to  claim 17 , wherein the nucleic acid sequence is SEQ ID NO. 2.  
     
     
         22 . The use according to  claim 17 , wherein the rational design includes structure/function analysis.  
     
     
         23 . The use according to  claim 22 , wherein the structure/function analysis includes one or more technique selected from the group consisting of DNA shuffling, enhanced selective mutagenesis and phage display.  
     
     
         24 . Use of a receptor protein having specific binding affinity for a PR-5 protein having a lectin-like β barrel domain, as a primary screen to identify a therapeutic agent that is an agonist or an antagonist of all or part of the adiponectin targets in a mammalian cell.  
     
     
         25 . The use of  claim 24 , wherein the PR-5 receptor is PHO36.  
     
     
         26 . The use of  claim 24 , wherein the screen is carried out using a receptor that is in isolated form.  
     
     
         27 . The use of  claim 24 , wherein the screen is carried out using a cell line or tissue culture expressing the receptor.  
     
     
         28 . The use of  claim 27 , wherein the cell line or tissue culture is overexpressing the receptor.  
     
     
         29 . The use of  claim 27 , wherein the screen is carried out using a yeast cell line.  
     
     
         30 . The use of  claim 29 , wherein the yeast is overexpressing the receptor.