Fig. 2

Ligand binding sites and dimerization interface of LIMP-2 compared to apo LIMP-2 monomer structure. a Each subunit (cyan ribbons) of the LIMP-2 dimer has extensive conformational changes compared to those of the apo LIMP-2 monomer (gray ribbons, PDB code 4Q4F). The helical bundle of the second subunit (α4, α5, and α7 in green ribbons) is shown to indicate the location of dimer interface. b The PC-binding site at the hydrophobic tunnel. The head group of bound PC displaces the α9 helix from its position in the apo structure, and interacts with K205, D272, and K330 (labeled). Hydrogen bonds are shown as dashes. Residues chosen for dimerization interfering mutations (H150 and F151) are indicated. c Extensive conformational changes observed surrounding the CLR-binding site. Residues V415 and A379, the equivalent residue proposed to be in the cholesterol path in SR-B1, are highlighted. Regions that are affected by CLR binding are labeled. d The hydrophobic tunnel of the apo LIMP-2 (gray mesh) is significantly different in shape and location from that of the LIMP-2 dimer (cyan solid surface) upon CLR and PC binding. e Hydrophobic cleft and the putative bound PC fragment, with contacting residues side chains shown in sticks. Equivalent residues that are important for HDL uptake by SR-BI or fatty acid or oxLDL uptake by CD36 are colored orange on the main chain. f The expansive mannose-6 glycans (M6D), P-Man9GlcNAc2 at N325, contribute to dimer interactions. Hydrogen bonds involving N-glycan are shown in dashes