PDBsum entry 1gwb

Blood clotting

PDB id: 1gwb

Contents

Protein chains

266 a.a. *

Ligands

ACY

NAG ×3

SO4

Metals

_PT ×4

Waters ×143

* Residue conservation analysis

PDB id:

1gwb

Name:

Blood clotting

Title:

Structure of glycoprotein 1b

Structure:

Platelet glycoprotein ib alpha chain. Chain: a, b. Fragment: n-terminal domain, residues 16-296. Synonym: gp-ib alpha, gpiba, cd42b-alpha, cd42b. Other_details: tyr 292,294,295 modified to tyrosine-o-sulphonic acid

Source:

Homo sapiens. Human. Organism_taxid: 9606

Biol. unit:

Monomer (from PDB file)

Resolution:

2.80Å R-factor: 0.245 R-free: 0.274

Authors:

J.Emsley,S.Uff,K.J.M.Clemetson,J.M.Clemetson,T.Harrison

Key ref:

S.Uff et al. (2002). Crystal structure of the platelet glycoprotein Ib(alpha) N-terminal domain reveals an unmasking mechanism for receptor activation. J Biol Chem, 277, 35657-35663. PubMed id: 12087105 DOI: 10.1074/jbc.M205271200

Date:

14-Mar-02 Release date: 06-Feb-03

Protein chains

P07359  (GP1BA_HUMAN) -  Platelet glycoprotein Ib alpha chain from Homo sapiens

Seq: 652 a.a.

Struc: 266 a.a.

DOI no: 10.1074/jbc.M205271200

J Biol Chem 277:35657-35663 (2002)

PubMed id: 12087105

Crystal structure of the platelet glycoprotein Ib(alpha) N-terminal domain reveals an unmasking mechanism for receptor activation.

S.Uff, J.M.Clemetson, T.Harrison, K.J.Clemetson, J.Emsley.

ABSTRACT

Glycoprotein Ib (GPIb) is a platelet receptor with a critical role in mediating the arrest of platelets at sites of vascular damage. GPIb binds to the A1 domain of von Willebrand factor (vWF-A1) at high blood shear, initiating platelet adhesion and contributing to the formation of a thrombus. To investigate the molecular basis of GPIb regulation and ligand binding, we have determined the structure of the N-terminal domain of the GPIb(alpha) chain (residues 1-279). This structure is the first determined from the cell adhesion/signaling class of leucine-rich repeat (LRR) proteins and reveals the topology of the characteristic disulfide-bonded flanking regions. The fold consists of an N-terminal beta-hairpin, eight leucine-rich repeats, a disulfide-bonded loop, and a C-terminal anionic region. The structure also demonstrates a novel LRR motif in the form of an M-shaped arrangement of three tandem beta-turns. Negatively charged binding surfaces on the LRR concave face and anionic region indicate two-step binding kinetics to vWF-A1, which can be regulated by an unmasking mechanism involving conformational change of a key loop. Using molecular docking of the GPIb and vWF-A1 crystal structures, we were also able to model the GPIb.vWF-A1 complex.

Selected figure(s)

Figure 1.
Fig. 1. Overall topology of the GPIb N-terminal domain. Ribbon diagram of the topology viewed from the side and a 90° rotated view facing the concave surface of the leucine-rich repeats are shown. The three short 3[10] helices are colored light blue, and the helix in the C-terminal flank is colored dark blue. Convex face -strands are colored green, and concave face -strands are colored gray. Five expressed BSS mutations, which cause loss of vWF binding, are shown as black balls. L57F and C65R localize to LRR2 with L129P, A156V, and L179del localized to the LRR5, LRR6, and LRR7 -strands respectively. The regulatory (R)-loop is colored orange with activating platelet-type von Willebrand disease mutations G233V and M239V indicated as orange balls. The anionic region is colored red with the molecular structure of the sulfated tyrosine residues 276, 278, and 279 shown in full.

Figure 3.
Fig. 3. Fine structure of the GPIb R-loop and anionic region. a and b, the R-loop and -strands from the concave face viewed from two orientations related by 90° rotation are shown. Key residues are labeled including platelet-type von Willebrand disease mutations G233V and M239V and the Bernard-Soulier syndrome mutation A156V. c, fine structure of the GPIb anionic region. Key residues in the anionic region (residues 269-279) are indicated showing the interactions with the disulfide loop and -turn repeat motif from LRR8. The backbone of the anionic region is colored red, the disulfide loop is colored dark green, and the LRR8 is colored blue. Key hydrogen bonding/electrostatic interactions are indicated as dotted blue lines.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 35657-35663) copyright 2002.

Figures were selected by an automated process.