title: Synthesis and assembly of functional high molecular weight adiponectin multimers in an engineered strain of Escherichia coli.
abstract: Adiponectin has many beneficial effects on cardiovascular and obesity-related disorders. It is part of a class of proteins that contains short collagenous domains, along with surfactant proteins A and D, and complement protein C1q. This class of biomacromolecules requires post-translational modifications to form biologically active assemblies. By introducing a set of post-translational modifying enzymes into  Escherichia coli , we have created a prokaryotic expression system that functionally assembles adiponectin, as assessed by the ability of produced adiponectin multimers to suppress human endothelial cell apoptosis. This study represents the first example of the assembly of functional high order multimers of any member of this class of proteins outside of eukaryotic cells. Furthermore, the results give fundamental insight into the process of assembly such as the necessity and sufficiency of various post-translational steps for functional assembly. We expect that fine-tuning of the expression system will allow for efficient production and functional assembly of biomolecules that assemble via short collagenous domains.
authors.affiliation: Department of Bioengineering, School of Medicine, Stanford University, Stanford, California 94305, United States.
authors.forename: Sheng
authors.initials: S
authors.lastname: Ding
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Pinkas
authors.forename: Annelise E
authors.initials: AE
authors.lastname: Barron
mesh_terms: D052242:Adiponectin / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D017209:Apoptosis; D002470:Cell Survival; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry* / Q000378:metabolism; D005057:Eukaryotic Cells / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D008970:Molecular Weight; D015202:Protein Engineering; D011499:Protein Processing, Post-Translational
chemical_list: D052242:Adiponectin; D046911:Macromolecular Substances