Organization and dynamics of the N-terminal domain of chemokine receptor CXCR1 in reverse micelles: Effect of graded hydration

Arunima Chaudhuri, Pritam Basu, Sourav Haldar, Mamata Kombrabail, G. Krishnamoorthy, Krishna Rajarathnam, Amitabha Chattopadhyay

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Water plays a fundamental role in the folding, structure, dynamics, and function of proteins and peptides. The extracellular N-terminal domain of chemokine receptors is crucial in mediating binding affinity, receptor selectivity, and regulating function. The flexible N-terminal domain becomes ordered in membranes and membrane-mimetic assemblies, thereby indicating that the membrane could play an important role in regulating CXC chemokine receptor 1 (CXCR1) function. In view of the role of hydration in lipid-protein interactions in membranes, we explored the organization and dynamics of a 34-mer peptide of the CXCR1 N-terminal domain in reverse micelles by utilizing a combination of fluorescence-based approaches and circular dichroism spectroscopy. Our results show that the secondary structure adopted by the CXCR1 N-domain is critically dependent on hydration. The tryptophan residues of the CXCR1 N-domain experience motional restriction and exhibit red edge excitation shift (REES) upon incorporation in reverse micelles. REES and fluorescence lifetime exhibit reduction with increasing reverse micellar hydration. Time-resolved fluorescence anisotropy measurements reveal the effect of hydration on peptide rotational dynamics. Taken together, these results constitute the first report demonstrating modulation in the organization and dynamics of the N-terminal domain of a chemokine receptor in a membrane-like environment of varying hydration. We envisage that these results are relevant in the context of hydration in the function of G protein-coupled receptors.

Original languageEnglish (US)
Pages (from-to)1225-1233
Number of pages9
JournalJournal of Physical Chemistry B
Volume117
Issue number5
DOIs
StatePublished - Feb 7 2013

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

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