PDBsum entry 4rtd

Lipid binding protein

PDB id: 4rtd

Contents

Protein chain

1122 a.a.

PDB id:

4rtd

Name:

Lipid binding protein

Title:

Escherichia coli alpha-2-macroglobulin activated by porcine elastase

Structure:

Uncharacterized lipoprotein yfhm. Chain: a. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 83333. Strain: k12. Gene: b2520, jw2504, yfhm. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

3.65Å R-factor: 0.180 R-free: 0.238

Authors:

C.D.Fyfe,R.Grinter,A.W.Roszak,I.Josts,R.J.Cogdell,D.Walker

Key ref:

C.D.Fyfe et al. (2015). Structure of protease-cleaved Escherichia coli α-2-macroglobulin reveals a putative mechanism of conformational activation for protease entrapment. Acta Crystallogr D Biol Crystallogr, 71, 1478-1486. PubMed id: 26143919 DOI: 10.1107/S1399004715008548

Date:

14-Nov-14 Release date: 15-Jul-15

Protein chain

P76578  (YFHM_ECOLI) -  Alpha-2-macroglobulin from Escherichia coli (strain K12)

Seq: 1653 a.a.

Struc: 1122 a.a.*

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

DOI no: 10.1107/S1399004715008548

Acta Crystallogr D Biol Crystallogr 71:1478-1486 (2015)

PubMed id: 26143919

Structure of protease-cleaved Escherichia coli α-2-macroglobulin reveals a putative mechanism of conformational activation for protease entrapment.

C.D.Fyfe, R.Grinter, I.Josts, K.Mosbahi, A.W.Roszak, R.J.Cogdell, D.M.Wall, R.J.Burchmore, O.Byron, D.Walker.

ABSTRACT

Bacterial α-2-macroglobulins have been suggested to function in defence as broad-spectrum inhibitors of host proteases that breach the outer membrane. Here, the X-ray structure of protease-cleaved Escherichia coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. In this competitive mechanism, protease cleavage of the bait-region domain results in the untethering of an intrinsically disordered region of this domain which disrupts native interdomain interactions that maintain E. coli α-2-macroglobulin in the inactivated form. The resulting global conformational change results in entrapment of the protease and activation of the thioester bond that covalently links to the attacking protease. Owing to the similarity in structure and domain architecture of Escherichia coli α-2-macroglobulin and human α-2-macroglobulin, this protease-activation mechanism is likely to operate across the diverse members of this group.