Table of Contents
International Journal of Peptides
Volume 2012, Article ID 634769, 14 pages
Review Article

Proline Rich Motifs as Drug Targets in Immune Mediated Disorders

1Department of Oral Pathology, Medicine and Radiology, Indiana University School of Dentistry, Indiana University Purdue University at Indianapolis 1121 West Michigan Street, DS290, Indianapolis, IN 46268, USA
2Department of Biochemistry and Molecular Biology and School of Informatics, Indiana University School of Medicine, Indiana University Purdue University at Indianapolis, Indianapolis, IN, USA

Received 29 December 2011; Accepted 15 February 2012

Academic Editor: Jean-Marie Zajac

Copyright © 2012 Mythily Srinivasan and A. Keith Dunker. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The current version of the human immunome network consists of nearly 1400 interactions involving approximately 600 proteins. Intermolecular interactions mediated by proline-rich motifs (PRMs) are observed in many facets of the immune response. The proline-rich regions are known to preferentially adopt a polyproline type II helical conformation, an extended structure that facilitates transient intermolecular interactions such as signal transduction, antigen recognition, cell-cell communication and cytoskeletal organization. The propensity of both the side chain and the backbone carbonyls of the polyproline type II helix to participate in the interface interaction makes it an excellent recognition motif. An advantage of such distinct chemical features is that the interactions can be discriminatory even in the absence of high affinities. Indeed, the immune response is mediated by well-orchestrated low-affinity short-duration intermolecular interactions. The proline-rich regions are predominantly localized in the solvent-exposed regions such as the loops, intrinsically disordered regions, or between domains that constitute the intermolecular interface. Peptide mimics of the PRM have been suggested as potential antagonists of intermolecular interactions. In this paper, we discuss novel PRM-mediated interactions in the human immunome that potentially serve as attractive targets for immunomodulation and drug development for inflammatory and autoimmune pathologies.