Structure-function studies on PEDF. A noninhibitory serpin with neurotrophic activity

Abstract

The neuronal differentiating and survival activities and presence of PEDF next to the neural retina support the idea that this serpin plays a neurotrophic role in vivo. The knowledge of the PEDF structure has provided information on the determinants for the noninhibitory and neurotrophic activities. PEDF has characteristics of a substrate rather than an inhibitor of serine proteases. Further studies are needed to identify the missing structural elements on PEDF that would confer serpin inhibitory activity. An N-terminus peptide region provides the neurotrophic function to the PEDF protein while other structural characteristics are dispensable (e.g. signal peptide, oligosaccharides on the polypeptide backbone, serpin exposed loop). During evolution PEDF might have lost its inhibitory activity and gained its neurotrophic function. Particular activities on other serpins have been reported (e.g. angiotensinogen, maspin, etc.). PEDF is an example of the separation of inhibitory and particular activities in a serpin.