S. Rothemund et al., A new class of hexahelical insect proteins revealed as putative carriers of small hydrophobic ligands, STRUCT F D, 7(11), 1999, pp. 1325-1332
Background: THP12 is an abundant and extraordinarily hydrophilic hemolymph
protein from the mealworm Tenebrio molitor and belongs to a group of small
insect proteins with four highly conserved cysteine residues. Despite their
sequence homology to odorant-binding proteins and pheromone-binding protei
ns, the function of these proteins is unclear.
Results: The first three-dimensional structure of THP12 has been determined
by multidimensional NMR spectroscopy. The protein has a nonbundle helical
structure consisting of six a helices. The arrangement of the a helices has
a 'baseball glove' shape. In addition to the hydrophobic core, electrostat
ic interactions make contributions to the overall stability of the protein.
NMR binding studies demonstrated the binding of small hydrophobic ligands
to the single hydrophobic groove in THP12. Comparing the structure of THP12
with the predicted secondary structure of homologs reveals a common fold f
or this new class of insect proteins. A search with the program DALI reveal
ed extensive similarity between the three-dimensional structure of THP12 an
d the N-terminal domain (residues 1-95) of recoverin, a member of the famil
y of calcium-binding EF-hand proteins.
Conclusions: Although the biological function of this new class of proteins
is as yet undetermined, a general role as a-helical carrier proteins for s
mall hydrophobic ligands, such as fatty acids or pheromones, is proposed on
the basis of NMR-shift perturbation spectroscopy.