Multifunctionality and mechanism of ligand binding in a mosquito antiinflammatory protein
Journal Article
·
· Proc. Natl. Acad. Sci. USA
The mosquito D7 salivary proteins are encoded by a multigene family related to the arthropod odorant-binding protein (OBP) superfamily. Forms having either one or two OBP domains are found in mosquito saliva. Four single-domain and one two-domain D7 proteins from Anopheles gambiae and Aedes aegypti (AeD7), respectively, were shown to bind biogenic amines with high affinity and with a stoichiometry of one ligand per protein molecule. Sequence comparisons indicated that only the C-terminal domain of AeD7 is homologous to the single-domain proteins from A. gambiae, suggesting that the N-terminal domain may bind a different class of ligands. Here, we describe the 3D structure of AeD7 and examine the ligand-binding characteristics of the N- and C-terminal domains. Isothermal titration calorimetry and ligand complex crystal structures show that the N-terminal domain binds cysteinyl leukotrienes (cysLTs) with high affinities (50-60 nM) whereas the C-terminal domain binds biogenic amines. The lipid chain of the cysLT binds in a hydrophobic pocket of the N-terminal domain, whereas binding of norepinephrine leads to an ordering of the C-terminal portion of the C-terminal domain into an alpha-helix that, along with rotations of Arg-176 and Glu-268 side chains, acts to bury the bound ligand.
- Research Organization:
- Argonne National Laboratory (ANL)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1005551
- Journal Information:
- Proc. Natl. Acad. Sci. USA, Journal Name: Proc. Natl. Acad. Sci. USA Journal Issue: (10) ; 03, 2009 Vol. 106; ISSN PNASA6; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- ENGLISH
Similar Records
A mosquito hemolymph odorant-binding protein family member specifically binds juvenile hormone
Functional and structural similarities of D7 proteins in the independently-evolved salivary secretions of sand flies and mosquitoes
Structure of an Odorant-Vinding Protein form the Mosquito Aedes aegypti Suggests a Binding Pocket Covered by a pH-Sensitive
Journal Article
·
Thu Sep 14 20:00:00 EDT 2017
· Journal of Biological Chemistry
·
OSTI ID:1400290
Functional and structural similarities of D7 proteins in the independently-evolved salivary secretions of sand flies and mosquitoes
Journal Article
·
Thu Mar 28 20:00:00 EDT 2019
· Scientific Reports
·
OSTI ID:1515299
Structure of an Odorant-Vinding Protein form the Mosquito Aedes aegypti Suggests a Binding Pocket Covered by a pH-Sensitive
Journal Article
·
Fri Dec 30 23:00:00 EST 2011
· PLoS One
·
OSTI ID:1042254