Novel p65 binding glucocorticoid-induced leucine zipper peptide suppresses experimental autoimmune encephalomyelitis

Mythily Srinivasan, Srihari Janardhanam

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Multiple sclerosis (MS) is a neurological disease characterized by inflammatory demyelination in the brain and spinal cord. The immune-mediated inflammation involves well orchestrated intermolecular interactions that exhibit rapid binding kinetics. The binding interfaces of transient interactions frequently include proline residues that favor an extended conformation for molecular recognition. Linear interface peptides are excellent lead inhibitors of specific protein-protein interactions because only small segments of the interface contribute to the binding. Glucocorticoid-induced leucine zipper (GILZ), a recently identified molecule exhibits potent anti-inflammatory properties. Mechanistically, a proline-rich segment in the carboxyl terminus of GILZ physically binds the p65 subunit of nuclear factor-κB and inhibits the transactivation of inflammatory cytokines. Integrating knowledge derived from the mechanism of action of GILZ with in silico structure prediction identified an immunomodulatory peptide, the GILZ-P. Treatment with GILZ-P exhibited therapeutic efficacy in experimental autoimmune encephalomyelitis, a model for human MS.

Original languageEnglish (US)
Pages (from-to)44799-44810
Number of pages12
JournalJournal of Biological Chemistry
Volume286
Issue number52
DOIs
StatePublished - Dec 30 2011

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Leucine Zippers
Autoimmune Experimental Encephalomyelitis
Glucocorticoids
Peptides
Proline
Multiple Sclerosis
Molecular Conformation
Molecular recognition
Demyelinating Diseases
Computer Simulation
Transcriptional Activation
Conformations
Brain
Spinal Cord
Proteins
Anti-Inflammatory Agents
Cytokines
Inflammation
Molecules
Kinetics

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Novel p65 binding glucocorticoid-induced leucine zipper peptide suppresses experimental autoimmune encephalomyelitis. / Srinivasan, Mythily; Janardhanam, Srihari.

In: Journal of Biological Chemistry, Vol. 286, No. 52, 30.12.2011, p. 44799-44810.

Research output: Contribution to journalArticle

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