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Figure 2.
Figure 2. Tim-3 Possesses a Unique Modification of the
Immunoglobulin Domain
(A) Comparison of murine Tim-3 IgV
domain and classical IgV domain. Left, ribbon diagram of murine
PD-1 structure (1NPU), showing the classical IgV fold in which
CC′ and FG loops are located at the opposite ends of the
domain (Zhang et al., 2004). Middle, overall structure of Tim-3
IgV, showing the “cleft” formed by the CC′ and FG loops.
Right, expanded view of the cleft, detailing the stabilizing
interactions. The β strands are labeled with capital letters.
Disulfide bonds are represented by green sticks, and four
additional cysteines that form two extra intramolecular
disulfide bonds in the cleft are labeled. Residues involved in
hydrogen bonding and ionic interactions are denoted as sticks
and are labeled. The hydrogen bonds and salt bridge are
highlighted by red dash lines.
(B) Alignment of the IgV
domain sequences of Tim family members. The β strands are
denoted as underlined segments in murine Tim-3. The conserved
residues are shaded red, and residues with similar properties
are labeled red. Six invariant cysteines within the family are
labeled. Three pairs of cysteines, i.e., Cys-38 and Cys-111
(black), Cys-52 and Cys-63 (blue), and Cys-58 and Cys-110 (red),
form three disulfide bonds. Residues bearing potential N- and
O-glycans are highlighted with a blue triangle and numbered.
Residues that contribute to ligand binding of Tim-3 are
highlighted with pink triangle and numbered.
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