Structural determinants of MIF functions in CXCR2-mediated inflammatory and atherogenic leukocyte recruitment.

ABSTRACT: We have recently identified the archaic cytokine macrophage migration inhibitory factor (MIF) as a non-canonical ligand of the CXC chemokine receptors CXCR2 and CXCR4 in inflammatory and atherogenic cell recruitment. Because its affinity for CXCR2 was particularly high, we hypothesized that MIF may feature structural motives shared by canonical CXCR2 ligands, namely the conserved N-terminal Glu-Leu-Arg (ELR) motif. Sequence alignment and structural modeling indeed revealed a pseudo-(E)LR motif (Asp-44-X-Arg-11) constituted by non-adjacent residues in neighboring loops but with identical parallel spacing as in the authentic ELR motif. Structure-function analysis demonstrated that mutation of residues R11, D44, or both preserve proper folding and the intrinsic catalytic property of MIF but s

SUBMITTER: Weber C 

PROVIDER: S-EPMC2566990 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature