19th-banner-rev.gif

Albany 2013: Book of Abstracts

category image Albany 2013
Conversation 18
June 11-15 2013
©Adenine Press (2012)

Role of free Cysteines in leptin receptor

Leptin, a 16 kDa adipocytic peptide hormone (product of ob gene) is known to play a key role in the control of body weight and exerts its influence by binding to its long form receptor (Ob-Rb). Ob-Rb belongs to class I cytokine receptor superfamily and consists of an extracellular, transmembrane and an intracellular domain. Cysteines including free and disulphide bonded are known to play a significant role in recognition of leptin by its receptor and is known to be highly conserved in different organisms including human, macaca, mouse, dog, sheep, zebrafish and medaca.

Recently the crystal structure of Leptin binding domain of human Leptin receptor has been determined (Carpenter et al, 2012). Using the structural data, we analysed the role of free cysteines in leptin binding domain of leptin receptor through docking studies using Rosettadock. The conserved free cysteines namely Cys-604, Cys-613 were mutated to alanines and this resulted in drastic change in the binding orientation of leptin and its receptor. Based on computational analysis we propose that cysteines either free or involved in disulphide bridges might play a crucial role during signaling and might be the primary determinant of leptin-receptor interactions, the details of which will be discussed. Currently, understanding the structural basis of leptin and its binding to leptin receptor gains lot of significance since it might pave way for designing inhibitors that might be used in controlling obesity.

References

Carpenter, B., Hemsworth, G. R., Wu, Z., Maamra, M., Strasburger, C. J., Ross, R. J., and Artymiuk, P . J. Structure of the Human Obesity Receptor Leptin-Binding Domain Reveals the Mechanism of Leptin Antagonism by a Monoclonal Antibody. Structure 20, 487–497 (2012)

R.Karthick1
Gokul Raghunath2
Sharmila Anishetty2
R.Malathi1

1 University of Madras
2 Anna University
Chennai, India

Ph: +91-44-24547062
Fx: +91-44-24540709
r_malathi@hotmail.com