PDBsum entry 2j0r

Transport protein

PDB id: 2j0r

Contents

Protein chain

331 a.a. *

Ligands

EDO ×5

PEG ×3

PGE

1PE

12P

Waters ×134

* Residue conservation analysis

PDB id:

2j0r

Name:

Transport protein

Title:

Structure of the haem-chaperone proteobacteria-protein hems

Structure:

Hemin transport protein hems. Chain: a. Synonym: hems. Engineered: yes

Source:

Yersinia enterocolitica. Organism_taxid: 630. Strain: wa-c. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.90Å R-factor: 0.191 R-free: 0.233

Authors:

S.Schneider,K.H.Sharp,P.D.Barker,M.Paoli

Key ref:

S.Schneider et al. (2006). An induced fit conformational change underlies the binding mechanism of the heme transport proteobacteria-protein HemS. J Biol Chem, 281, 32606-32610. PubMed id: 16943192 DOI: 10.1074/jbc.M607516200

Date:

04-Aug-06 Release date: 29-Aug-06

Protein chain

P31517  (HEMS_YEREN) -  Hemin transport protein HemS from Yersinia enterocolitica

Seq: 345 a.a.

Struc: 331 a.a.*

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

DOI no: 10.1074/jbc.M607516200

J Biol Chem 281:32606-32610 (2006)

PubMed id: 16943192

An induced fit conformational change underlies the binding mechanism of the heme transport proteobacteria-protein HemS.

S.Schneider, K.H.Sharp, P.D.Barker, M.Paoli.

ABSTRACT

Bacteria rely on their environment and/or host to acquire iron and have evolved specialized systems to sequester and transport heme. The heme uptake system HemRSTUV is common to proteobacteria, and a major challenge is to understand the molecular mechanism of heme binding and transfer between the protein molecules that underlie this heme transport relay process. In the Gram-negative pathogen Yersinia enterocolitica, the HemRSTUV system culminates with the cytoplasmic recipient HemS, which stores and delivers heme for cellular needs. HemS belongs to a family of proteins essential and unique to proteobacteria. Here we report on the binding mechanism of HemS based on structural data from its apo- and ligand-loaded forms. This heme carrier protein associates with its cargo through a novel, partly preformed binding pocket, formed between a large beta-sheet dome and a three-helix subdomain. In addition to a histidine interacting with the iron, the complex is stabilized by a distal non-coordinating arginine that packs along the porphyrin plane and extensive electrostatic contacts that firmly anchor the heme propionate groups within the protein. Comparison of apo- and ligand-bound HemS crystal structures reveals striking conformational changes that underlie a "heme-induced fit" binding mechanism. Local shifts in amino acid positions combine with global, rigid body-like domain movements, and together, these bring about a switch from an open, apo-form to a closed, bound state. This is the first report in which both liganded and unliganded forms of a heme transport protein are described, thus providing penetrating insights into its mechanism of heme binding and release.

Selected figure(s)

Figure 2.
FIGURE 2. Heme-protein interactions. A, heme-binding pocket in the heme-HemS complex. Residues provided by the N-terminal domain are colored in blue, and residues provided by the C-terminal domain are in red. His-196 stems from the beginning of helix 7 and coordinates the iron. Arg-102 extends over the porphyrin plane next to Leu-94. B, residues interacting with the heme propionates. An extensive electrostatic/polar network of seven direct and two water-mediated (not shown) contacts firmly anchor the propionate groups.

Figure 4.
FIGURE 4. The HemS conformational switch between apo, open state and liganded, closed state. The superposition was prepared as in Fig. 3. The heme complex is shown in green, and the apo-structure is shown in gold. The superposition shows the global interdomain movements in HemS that effectively clamp the ligand in the binding site. N-domain, N-terminal domain; C-domain, C-terminal domain.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 32606-32610) copyright 2006.

Figures were selected by the author.