The Structure of NPC1L1(NTD).

<p>(A) NPC1L1(NTD) is represented as a ribbon diagram and the disulfide bonds are shown in yellow. Domain A is colored orange (α-helices), cyan (β-sheets), and gray (loops). α3 (red), α7 (blue), and the α8/β7 loop (green) surround the entrance of the cholesterol binding pocket. Domain B is colored magenta. (B) Superposition of NPC1L1(NTD) (yellow) and NPC1(NTD) (gray). Bound cholesterol in NPC1 is shown as a stick model. Regions around the entrance of the cholesterol binding pocket in NPC1L1 are colored red (α3), blue (α7), and green (α8/β7 loop). (C) Sequence alignment of NPC1L1(NTD) and NPC1(NTD). N-linked glycosylation sites are shaded gray. Residues lining the cholesterol binding pocket are shaded yellow in NPC1. In NPC1L1, residues within the interior of the closed cholesterol binding pocket are shaded blue, residues on the exterior of the closed cholesterol binding pocket are shaded green, and residues separating the interior from the exterior are shaded red. Regions around the entrance to the cholesterol binding pocket that change conformation are boxed. The secondary structure of NPC1L1(NTD) is shown below the sequence.