PDBsum entry: 1lqv

Blood clotting

PDB id: 1lqv

Contents

Protein chains

172 a.a. *

33 a.a. *

Ligands

NAG ×5

NDG

PTY ×2

Metals

_CA ×14

Waters ×429

* Residue conservation analysis

PDB id:

1lqv

Name:

Blood clotting

Title:

Crystal structure of the endothelial protein c receptor with phospholipid in the groove in complex with gla domain of pr

Structure:

Endothelial protein c receptor. Chain: a, b. Fragment: extracellular domain. Synonym: endothelial cell protein c receptor, activated pro receptor, apc receptor. Engineered: yes. Vitamin-k dependent protein c. Chain: c, d. Fragment: protein c gla domain.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Other_details: cleavage happened during crystallization and crystal contains only the n-terminal domain (gla domain) of c.

Biol. unit:

Dimer (from PQS)

Resolution:

1.60Å R-factor: 0.189 R-free: 0.222

Authors:

V.Oganesyan,N.Oganesyan,S.Terzyan,Q.Dongfeng,Z.Dauter,N.L.Es C.T.Esmon

Key ref:

V.Oganesyan et al. (2002). The crystal structure of the endothelial protein C receptor and a bound phospholipid. J Biol Chem, 277, 24851-24854. PubMed id: 12034704 DOI: 10.1074/jbc.C200163200

Date:

13-May-02 Release date: 19-Jun-02

Protein chains

Q9UNN8  (EPCR_HUMAN) -  Endothelial protein C receptor

Seq: 238 a.a.

Struc: 172 a.a.

Protein chains

P04070  (PROC_HUMAN) -  Vitamin K-dependent protein C

Seq: 461 a.a.

Struc: 33 a.a.*

* PDB and UniProt seqs differ at 9 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains C, D: E.C.3.4.21.69 - Protein C (activated).
• Reaction: Degradation of blood coagulation factors Va and VIIIa.

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (3 terms)
• Biological process: immune response (2 terms)
• Biochemical function: calcium ion binding (1 term)

DOI no: 10.1074/jbc.C200163200

J Biol Chem 277:24851-24854 (2002)

PubMed id: 12034704

The crystal structure of the endothelial protein C receptor and a bound phospholipid.

V.Oganesyan, N.Oganesyan, S.Terzyan, D.Qu, Z.Dauter, N.L.Esmon, C.T.Esmon.

ABSTRACT

The endothelial cell protein C receptor (EPCR) shares approximately 20% sequence identity with the major histocompatibility complex class 1/CD1 family of molecules, accelerates the thrombin-thrombomodulin-dependent generation of activated protein C, a natural anticoagulant, binds to activated neutrophils, and can undergo translocation from the plasma membrane to the nucleus. Blocking protein C/activated protein C binding to the receptor inhibits not only protein C activation but the ability of the host to respond appropriately to bacterial challenge, exacerbating both the coagulant and inflammatory responses. To understand how EPCR accomplishes these multiple tasks, we solved the crystal structure of EPCR alone and in complex with the phospholipid binding domain of protein C. The structures were strikingly similar to CD1d. A tightly bound phospholipid resides in the groove typically involved in antigen presentation. The protein C binding site is outside this conserved groove and is distal from the membrane-spanning domain. Extraction of the lipid resulted in loss of protein C binding, which could be restored by lipid reconstitution. CD1d augments the immune response by presenting glycolipid antigens. The EPCR structure is a model for how CD1d binds lipids and further suggests additional potential functions for EPCR in immune regulation, possibly including the anti-phospholipid syndrome.

Selected figure(s)

Figure 1.
Fig. 1. The rsEPCR molecule with a portion of the protein C Gla domain and a lipid molecule. In EPCR (yellow ribbon), two -helices and an eight-stranded -sheet create a groove that is filled with phospholipid (the space-filling balls in the center). Binding of Ca^2+ ions (magenta spheres) to the protein C Gla domain (green ribbon) exposes the N-terminal loop, which in the absence of EPCR interacts with the phospholipid surfaces on the membrane. There do not appear to be direct interactions between the protein C Gla domain and the lipid molecule located in the groove of rsEPCR. The model of the complex consists of residues 7-177 of rsEPCR and the first 33 residues of the protein C Gla domain (25, 26).

Figure 4.
Fig. 4. The amino acids participating in the interactions between the Gla domain of protein C and rsEPCR. The yellow portion is the interacting region of rsEPCR, the green portion is the interacting region of the protein C Gla domain, and the magenta balls represent the bound Ca^2+ ions. The lipid molecule is shown in black (25, 26).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 24851-24854) copyright 2002.

Figures were selected by the author.