Proline rich motifs as drug targets in immune mediated disorders

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number634769
JournalInternational Journal of Peptides
Volume2012
DOIs
StatePublished - 2012

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Immune System Diseases
Proline
Pharmaceutical Preparations
Signal transduction
Immunomodulation
Pathology
Cell Communication
Conformations
Signal Transduction
Antigens
Peptides
Communication
Proteins
polyproline

ASJC Scopus subject areas

  • Biochemistry

Cite this

Proline rich motifs as drug targets in immune mediated disorders. / Srinivasan, Mythily; Dunker, A.

In: International Journal of Peptides, Vol. 2012, 634769, 2012.

Research output: Contribution to journalArticle

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