Structure and isoforms of mouse leptin receptor. Ob-Rb contains the longest intracellular domain, which is crucial for leptin signaling. Ob-Ra, Ob-Rc and Ob-Rd contain only short cytoplasmic domains. Ob-Re is a secreted isoform of the leptin receptor, lacking transmembrane and cytoplasmic parts. Cytokine receptor homology module (CRH)2 is the main binding site for leptin on the Ob-R. The Ig-like and the FN-III domains are critically involved in Ob-R activation. The role of CRH1 remains to be determined [111, 112]. FNIII, fibronectin type III domain; Ig-like, immunoglobulin-like fold.