Figure 4.3.
Three-dimensional (3D) homology models of human RFC. A 3D model for human RFC is presented, based on structure alignments between RFC and LacY/GlpT and experimental data. (A) A side view of the RFC for which the extended C-terminal segment is truncated at Lys479. TMD1, TMD2, TMD4, and TMD5 of the N-terminal region and TMD7, TMD8, TMD10, and TMD11 of the C-terminal region are involved in formation of the hydrophilic binding site for anionic folates (colored sky blue). TMD3, TMD6, TMD9, and TMD12 are buried in the lipid bilayer and do not directly participate in substrate binding (colored green). Panel (A) also depicts key amino acids (shown in assorted colors) that may contribute to the binding pocket for anionic folate substrates, as described in the text. (B) A cytosolic view of only the TMD segments of the human RFC molecule so that the order of helix packing can be seen easily. TMD coloring is the same as described in (A). (C) Enhanced view of the hypothetical substrate-binding site comprising the same key amino acids depicted in (A), including Lys411, Ser313, Tyr281, and Arg373, as described in the text. Other residues that may contribute to the substrate-binding pocket are also shown and include Arg133, Ile134, Ala135, Tyr136, and Ser138. The physical distances between the αcarboxyl groups of Lys411, Ser313, Tyr281, and Arg373 are given in angstroms. This figure was originally published in The Journal of Biological Chemistry, by Hou et al. (2006). © The American Society for Biochemistry and Molecular Biology.