Vj. Licata et Da. Bernlohr, Surface properties of adipocyte lipid-binding protein: Response to lipid binding, and comparison with homologous proteins, PROTEINS, 33(4), 1998, pp. 577-589
Adipocyte lipid-binding protein (ALBP) is one of a family of intracellular
lipid-binding proteins (iLBPs) that bind fatty acids, retinoids, and other
hydrophobic ligands. The different members of this family exhibit a highly
conserved three dimensional structure; and where structures have been deter
mined both with (holo) and without (apo) bound lipid, observed conformation
al changes are extremely small (Banaszak, et al., 1994, Adv. Prot. Chem. 45
, 89; Bernlohr, et al., 1997, Annu. Rev. Nutr. 17, 277). We have examined t
he electrostatic, hydrophobic, and water accessible surfaces of ALBP in the
apo form and of hole forms with a variety of bound ligands. These calculat
ions reveal a number of previously unrecognized changes between apo and hol
e ALBP, including: 1) an increase in the overall protein surface area when
Ligand binds, 2) expansion of the binding cavity when ligand is bound, 3) c
lustering of individual residue exposure increases in the area surrounding
the proposed ligand entry portal, and 4) ligand-binding dependent variation
in the topology of the electrostatic potential in the area surrounding the
ligand entry portal. These focused analyses of the crystallographic struct
ures thus reveal a number of subtle but consistent conformational and surfa
ce changes that might serve as markers for differential targeting of protei
n-lipid complexes within the cell. Most changes are consistent from ligand
to ligand, however there are some ligand-specific changes. Comparable calcu
lations with intestinal fatty-acid-binding protein and other vertebrate iLB
Ps show differences in the electrostatic topology, hydrophobic topology, an
d in localized changes in solvent exposure near the ligand entry portal. Th
ese results provide a basis toward understanding the functional and mechani
stic differences among these highly structurally homologous proteins. Furth
er, they suggest that iLBPs from different tissues exhibit one of two predo
minant end-state structural distributions of the ligand entry portal. (C) 1
998 Wiley-Liss, Inc.