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Int J Pept. 2012;2012:634769. doi: 10.1155/2012/634769. Epub 2012 May 16.

Proline rich motifs as drug targets in immune mediated disorders.

Author information

  • 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.

Abstract

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.

PMID:
22666276
[PubMed]
PMCID:
PMC3362030
Free PMC Article
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