PDBsum entry 1g1r

Immune system, membrane protein

PDB id: 1g1r

Contents

Protein chain

160 a.a. *

Ligands

MAG-GAL-SIA-FUC ×3

MRD ×2

Metals

_CA ×4

* Residue conservation analysis

PDB id:

1g1r

Name:

Immune system, membrane protein

Title:

Crystal structure of p-selectin lectin/egf domains complexed with slex

Structure:

P-selectin. Chain: a, b, c, d. Fragment: lectin/egf domains. Synonym: granule membrane protein 140, gmp-140, padgem, cd62p, leukocyte-endothelial cell adhesion molecule 3, lecam3. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell: ovary [cho] cells.

Resolution:

3.40Å R-factor: 0.227 R-free: 0.322

Authors:

W.S.Somers,R.T.Camphausen

Key ref:

W.S.Somers et al. (2000). Insights into the molecular basis of leukocyte tethering and rolling revealed by structures of P- and E-selectin bound to SLe(X) and PSGL-1. Cell, 103, 467-479. PubMed id: 11081633 DOI: 10.1016/S0092-8674(00)00138-0

Date:

13-Oct-00 Release date: 13-Oct-01

Protein chains

P16109  (LYAM3_HUMAN) -  P-selectin from Homo sapiens

Seq: 830 a.a.

Struc: 160 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1016/S0092-8674(00)00138-0

Cell 103:467-479 (2000)

PubMed id: 11081633

Insights into the molecular basis of leukocyte tethering and rolling revealed by structures of P- and E-selectin bound to SLe(X) and PSGL-1.

W.S.Somers, J.Tang, G.D.Shaw, R.T.Camphausen.

ABSTRACT

P-, E- and L-selectin constitute a family of cell adhesion receptors that mediate the initial tethering and rolling of leukocytes on inflamed endothelium as a prelude to their firm attachment and extravasation into tissues. The selectins bind weakly to sialyl Lewisx (SLe(X))-like glycans, but with high-affinity to specific glycoprotein counterreceptors, including PSGL-1. Here, we report crystal structures of human P- and E-selectin constructs containing the lectin and EGF (LE) domains co-complexed with SLe(X). We also present the crystal structure of P-selectin LE co-complexed with the N-terminal domain of human PSGL-1 modified by both tyrosine sulfation and SLe(X). These structures reveal differences in how E- and P-selectin bind SLe(X) and the molecular basis of the high-affinity interaction between P-selectin and PSGL-1.

Selected figure(s)

Figure 1.
Figure 1. Comparison of P-LE to the Structure of E-LE ([17])(A) Ribbon representation of the optimal superposition of P-LE and the previously described E-LE structure showing overall similarity. P-LE is in blue and E-LE is in green. The bound calcium ions in the two structures are precisely superimposed and are represented as a single yellow sphere.(B) A ball and stick representation of the superposition of P-LE and E-LE residues in the vicinity of the SLe^X binding site. The coloring scheme and superposition of calcium ions is identical to that in Figure 1A. For clarity, only interactions with the bound calcium in E-LE are shown as dashed lines. The stabilizing hydrogen bond between Arg97 and Asp100 in E-selectin is also shown as a dashed line. For residues that differ between E- and P-selectin, E-selectin residues are listed first. All structure figures were produced with MOLSCRIPT ( [20]) and RASTER3D ( [27]) except where noted.

Figure 6.
Figure 6. Structure of the P-LE/SGP-3 Complex and Binding Interactions Involving Tys Residues(A) Ribbon/stick representation of the P-LE/SGP-3 structure superimposed on the unliganded structure of P-LE. The unliganded structure of P-LE is shown in blue, complexed P-LE in purple, and SGP-3 in orange. The bound strontium ion in the P-LE/SGP-3 complex is directly superimposed over the calcium ion in unliganded P-LE and is shown as a green sphere. The MPD molecule that is found at the lectin-EGF domain interface in the P-LE/SGP-3 complex is shown in dark blue.(B) Stereo view of a close-up of P-LE/SGP-3 interactions in the region of Tys7 (in orange) illustrating the hydrogen bonding network with P-LE (purple). The sulfur atom in Tys7 is shown in yellow.(C) Stereo view of a close-up of the P-LE/SGP-3 interaction in the region of Tys10 and the Fuc binding site illustrating the change in conformation and binding contacts for the Asn83 to Asp89 loop within P-LE. Uncomplexed P-LE is shown in blue and P-LE complexed with SGP-3 is shown in purple. SGP-3 residues are shown in orange (the sulfur atom of Tys10 is in yellow) and the bound strontium ion is shown as a green sphere. The portion of SGP-3 omitted for clarity is shown as an orange ellipse.

The above figures are reprinted by permission from Cell Press: Cell (2000, 103, 467-479) copyright 2000.

Figures were selected by an automated process.