6U66

Structure of the trimeric globular domain of Adiponectin

Summary for 6U66

• Entry DOI: 10.2210/pdb6u66/pdb
• Descriptor: Adiponectin, CALCIUM ION, SODIUM ION, ... (4 entities in total)
• Functional Keywords: hormone, globular domain
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 3
• Total formula weight: 48968.31

Authors

Pascolutti, R.,Kruse, A.C.,Erlandson, S.C.,Burri, D.J.,Zheng, S. (deposition date: 2019-08-29, release date: 2020-01-22, Last modification date: 2023-10-11)

Primary citation

Pascolutti, R.,Erlandson, S.C.,Burri, D.J.,Zheng, S.,Kruse, A.C.
Mapping and engineering the interaction between adiponectin and T-cadherin.
J.Biol.Chem., 295:2749-2759, 2020

PubMed Abstract: Adiponectin is a highly abundant protein hormone secreted by adipose tissue. It elicits diverse biological responses, including anti-diabetic, anti-inflammatory, anti-tumor, and anti-atherosclerotic effects. Adiponectin consists of a globular domain and a collagen-like domain, and it occurs in three major oligomeric forms that self-assemble: trimers, hexamers, and high-molecular-weight oligomers. Adiponectin has been reported to bind to two seven-transmembrane domain receptors, AdipoR1 and AdipoR2, as well as to the protein T-cadherin, which is highly expressed in the cardiovascular system and binds only the high-molecular-weight form of adiponectin. The molecular mechanisms underlying this specificity remain unclear. Here we used a combination of X-ray crystallography and protein engineering to define the details of adiponectin's interaction with T-cadherin. We found that T-cadherin binds to the globular domain of adiponectin, relying on structural stabilization of this domain by bound metal ions. Moreover, we show that the adiponectin globular domain can be engineered to enhance its binding affinity for T-cadherin. These results help to define the molecular basis for the interaction between adiponectin and T-cadherin, and our engineered globular domain variants may be useful tools for further investigating adiponectin's functions.

PubMed: 31915248
DOI: 10.1074/jbc.RA119.010970

Experimental method

X-RAY DIFFRACTION (0.99 Å)