1. Volume 24, Issue 9, Pages 1590-1598 (September 2016)
Domain-Swapped Dimers of Intracellular Lipid-Binding Proteins: Evidence for Ordered Folding Intermediates 
Zahra Assar, Zahra Nossoni, Wenjing Wang, Elizabeth M. Santos, Kevin Kramer, Colin McCornack, Chrysoula Vasileiou, Babak Borhan, James H. Geiger 
Structure 
Volume 24, Issue 9, Pages (September 2016)
DOI: /j.str
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2. Structure 2016 24, 1590-1598DOI: (10.1016/j.str.2016.05.022)
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3. Figure 1
The Crystal Structures of hCRBPII Dimer Species and Comparison with Their Monomeric Structures
(A) Chain A of KLY60W (where only the Thr56 psi angle differs from the closed monomer form) with the electron density, contoured at 1.0 σ, of the hinge loop region encompassing amino acids 55–60. Residues 55–60 are highlighted. Atoms colored by type: N, blue; O, red; C, cyan. Color scheme retained unless otherwise noted.
(B) Chain B of the KLY60W mutant showing the electron density contoured at 1.0 σ of the hinge loop region encompassing amino acids 55–60. Residues 55–60 are highlighted (C, pink).
(C) The structure of the KLY60W dimer: In chain A (cyan), Trp60 is pointing inside the binding pocket, while in chain B (pink), Trp60 is pointing toward the solvent.
(D) An overlay of the dimeric (cyan) and monomeric (red) KLY60W mutant structures. Res56 for both structures is shown in sticks. The hinge loop region in the monomer and dimer is highlighted, showing the dramatic difference in the two structures.
Structure  , DOI: ( /j.str )
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4. Figure 2 A Comparison of Symmetric and Asymmetric hCRBPII Dimers
Res60 in all structures is shown as a stick model.
(A) An overlay of the asymmetric dimers: KLY60W (cyan) and Y60W (orange) showing that they are virtually identical.
(B) An overlay of the symmetric WT hCRBPII (purple) and Y60L (yellow) dimers.
(C) A comparison of the symmetric and asymmetric dimers. The C-terminal 76 amino acids of the Y60L (yellow) and chain A of the KLY60W (cyan) dimers are overlaid (on the left side of the figure). Both chains of the dimers are shown.
(D) The C-terminal 76 amino acids of the symmetric Y60L (yellow) and chain A (orange) and chain B (blue) of the Y60W dimers are overlaid, showing the large deviation of the N-terminal regions of the three chains.
Structure  , DOI: ( /j.str )
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5. Figure 3
Torsional Deviations Outside the Hinge-Loop Region Define the Relative Orientation of the Two Domains of the Dimer, with the Highest Deviation Seen in Asn59
The loss of the E72/Y60 hydrogen bond leads to a dimer without Ramachandran outliers.
(A) The WT (purple) and Y60L (yellow) dimers are overlaid. Inset, the hydrogen bond between Tyr60 and Glu72 compared to the flipped-out conformation of Leu60.
(B) The critical Tyr60 and Asn59 region in the WT hCRBPII dimer, showing the key phi/psi angles.
(C) The same region in the Y60L dimer, showing the flipped-out Leu60 and the key phi/psi angles. Comparison of the two shows how the large difference in the phi angle is compensated for in the psi angle, keeping the main chain of the two on a similar trajectory. This necessitates the large Ramachandran deviation in the psi angle of the WT hCRBPII dimer.
(D) Overlay of chain A of the E72A dimer (green) and the Y60L dimer (yellow). Note that both show residue 60 pointing toward the solvent.
(E) Overlay of the E72A chain A (purple) and WT (green) dimers. Inset shows that, without the E72/Y60 hydrogen bond, residue 60 is free to flip out, leading to a more relaxed dimer structure.
Structure  , DOI: ( /j.str )
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6. Figure 4 Model of folding in hCRBPII
The model hypothesizes that an open monomer folding intermediate leads to domain-swapped dimerization and requires proper relative orientation of the two halves of the open monomer: Left, the two A chains of an asymmetric dimer cannot dimerize due to severe steric clashes. Right, the A and B chains of the asymmetric dimer fit perfectly to form a stable, asymmetric dimer.
Structure  , DOI: ( /j.str )
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