Human adiponectin receptor AdipoR1 assumes closed and open structures

Area of Science:

• Biochemistry
• Structural Biology
• Molecular Endocrinology

Background:

• Human adiponectin receptors (AdipoR1 and AdipoR2) are critical targets for anti-diabetic therapies.
• Previous structural studies revealed AdipoR1 and AdipoR2 possess an internal closed cavity formed by seven transmembrane helices.

Purpose of the Study:

• To elucidate the structural basis of AdipoR1's functional mechanism.
• To investigate the conformational changes underlying AdipoR1 activity.

Main Methods:

• X-ray crystallography was employed to determine the structure of a D208A variant of AdipoR1.
• Re-analysis of existing wild-type AdipoR1 diffraction data was performed.

Main Results:

• The crystal structure of the D208A AdipoR1 variant revealed both closed and open conformations.
• The open form exhibits significant openings in the internal cavity, with distinct tilting of helices IV and V.
• Wild-type AdipoR1 exists as a mixture of closed (44%) and open (56%) forms.

Conclusions:

• The closed-open interconversion of AdipoR1 is a key feature of its structure.
• This conformational flexibility likely plays a significant role in AdipoR1's anti-diabetic signaling pathways.