PDBsum entry 2qy0

Hydrolase

PDB id: 2qy0

Contents

Protein chains

154 a.a. *

236 a.a. *

Ligands

GOL ×7

Waters ×160

* Residue conservation analysis

PDB id:

2qy0

Name:

Hydrolase

Title:

Active dimeric structure of the catalytic domain of c1r reveals enzyme-product like contacts

Structure:

Complement c1r subcomponent. Chain: a, c. Fragment: sushi-1 and sushi-2 domains, ccp1-ccp2. Engineered: yes. Complement c1r subcomponent. Chain: b, d. Fragment: peptidase s1 domain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: c1r. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.60Å R-factor: 0.213 R-free: 0.259

Authors:

J.Kardos,V.Harmat,A.Pallo,O.Barabas,K.Szilagyi,L.Graf,G.Naray-Szabo, Y.Goto,P.Zavodszky,P.Gal

Key ref:

J.Kardos et al. (2008). Revisiting the mechanism of the autoactivation of the complement protease C1r in the C1 complex: structure of the active catalytic region of C1r. Mol Immunol, 45, 1752-1760. PubMed id: 17996945 DOI: 10.1016/j.molimm.2007.09.031

Date:

13-Aug-07 Release date: 05-Feb-08

Protein chains

P00736  (C1R_HUMAN) -  Complement C1r subcomponent from Homo sapiens

Seq: 705 a.a.

Struc: 154 a.a.*

Protein chains

P00736  (C1R_HUMAN) -  Complement C1r subcomponent from Homo sapiens

Seq: 705 a.a.

Struc: 236 a.a.

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B, C, D: E.C.3.4.21.41 - complement subcomponent C1r.
• Reaction: Selective cleavage of Lys(or Arg)-|-Ile bond in complement subcomponent C1s to form the active form of C1s (EC 3.4.21.42).

DOI no: 10.1016/j.molimm.2007.09.031

Mol Immunol 45:1752-1760 (2008)

PubMed id: 17996945

Revisiting the mechanism of the autoactivation of the complement protease C1r in the C1 complex: structure of the active catalytic region of C1r.

J.Kardos, V.Harmat, A.Palló, O.Barabás, K.Szilágyi, L.Gráf, G.Náray-Szabó, Y.Goto, P.Závodszky, P.Gál.

ABSTRACT

C1r is a modular serine protease which is the autoactivating component of the C1 complex of the classical pathway of the complement system. We have determined the first crystal structure of the entire active catalytic region of human C1r. This fragment contains the C-terminal serine protease (SP) domain and the preceding two complement control protein (CCP) modules. The activated CCP1-CCP2-SP fragment makes up a dimer in a head-to-tail fashion similarly to the previously characterized zymogen. The present structure shows an increased number of stabilizing interactions. Moreover, in the crystal lattice there is an enzyme-product relationship between the C1r molecules of neighboring dimers. This enzyme-product complex exhibits the crucial S1-P1 salt bridge between Asp631 and Arg446 residues, and intermolecular interaction between the CCP2 module and the SP domain. Based on these novel structural information we propose a new split-and-reassembly model for the autoactivation of the C1r. This model is consistent with experimental results that have not been explained adequately by previous models. It allows autoactivation of C1r without large-scale, directed movement of C1q arms. The model is concordant with the stability of the C1 complex during activation of the next complement components.