Crystal structure of a single-chain trimer of human adiponectin globular domain

• Published in: FEBS letters Vol. 586; no. 6; pp. 912 - 917
• Main Authors: Min, Xiaoshan, Lemon, Bryan, Tang, Jie, Liu, Qiang, Zhang, Richard, Walker, Nigel, Li, Yang, Wang, Zhulun
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 23.03.2012
• Subjects: 5′-AMP-activated protein kinase; ACRP30; adipocyte complement-related protein of 30 kDa; Adiponectin; Adiponectin - chemistry; Adiponectin - genetics; Adiponectin - metabolism; AMPK; Animals; Calcium - metabolism; Calcium binding; Chinese hamster ovary; CHO; Crystallography, X-Ray; Humans; Mice; Models, Molecular; Molecular Sequence Data; ob/ob; obese mouse; PEG; polyethylene glycol; Protein Structure, Tertiary; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Single-chain globular domain; X-ray crystal structure; Single-chain globular domain; Calcium binding; PEG; ob/ob; AMPK; X-ray crystal structure; CHO; ACRP30; Adiponectin
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2012.02.024

► We solved the structure of a single-chain trimer of human adiponectiin globular domain. ► The structure revealed a trimeric topology similar to other C1q family proteins. ► The trimeric formation is rigidified by three intrinsic calcium ions. Adiponectin is increasingly recognized as a potential therapeutic agent for the treatment of diabetes and other metabolic diseases. It circulates in plasma as homotrimers and higher-order oliogomers of homotrimers. To facilitate the production of active recombinant adiponectin as a therapeutic tool, we designed a single-chain globular domain adiponectin (sc-gAd) in which three monomer sequences are linked together in tandem to form one contiguous polypeptide. Here, we present the crystal structure of human sc-gAd at 2.0Å resolution. The structure reveals a similar trimeric topology to that of mouse gAd protein. Trimer formation is further rigidified by three calcium ions.