PDBsum entry: 1a6z

Mhc class i complex

PDB id: 1a6z

Contents

Protein chains

272 a.a. *

99 a.a. *

Waters ×23

* Residue conservation analysis

PDB id:

1a6z

Name:

Mhc class i complex

Title:

Hfe (human) hemochromatosis protein

Structure:

Hfe. Chain: a, c. Engineered: yes. Beta-2-microglobulin. Chain: b, d

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organ: ovary. Gene: hfe. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell_line: cho. Organ: ovary

Biol. unit:

Dimer (from PQS)

Resolution:

2.60Å R-factor: 0.233 R-free: 0.277

Authors:

J.A.Lebron,M.J.Bennett,D.E.Vaughn,A.J.Chirino,P.M.Snow, G.A.Mintier,J.N.Feder,P.J.Bjorkman

Key ref:

J.A.Lebrón et al. (1998). Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor. Cell, 93, 111-123. PubMed id: 9546397 DOI: 10.1016/S0092-8674(00)81151-4

Date:

04-Mar-98 Release date: 23-Mar-99

Protein chains

Q30201  (HFE_HUMAN) -  Hereditary hemochromatosis protein

Seq: 348 a.a.

Struc: 272 a.a.

Protein chains

P61769  (B2MG_HUMAN) -  Beta-2-microglobulin

Seq: 119 a.a.

Struc: 99 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (8 terms)
• Biological process: immune response (8 terms)
• Biochemical function: protein binding (1 term)

DOI no: 10.1016/S0092-8674(00)81151-4

Cell 93:111-123 (1998)

PubMed id: 9546397

Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor.

J.A.Lebrón, M.J.Bennett, D.E.Vaughn, A.J.Chirino, P.M.Snow, G.A.Mintier, J.N.Feder, P.J.Bjorkman.

ABSTRACT

HFE is an MHC-related protein that is mutated in the iron-overload disease hereditary hemochromatosis. HFE binds to transferrin receptor (TfR) and reduces its affinity for iron-loaded transferrin, implicating HFE in iron metabolism. The 2.6 A crystal structure of HFE reveals the locations of hemochromatosis mutations and a patch of histidines that could be involved in pH-dependent interactions. We also demonstrate that soluble TfR and HFE bind tightly at the basic pH of the cell surface, but not at the acidic pH of intracellular vesicles. TfR:HFE stoichiometry (2:1) differs from TfR:transferrin stoichiometry (2:2), implying a different mode of binding for HFE and transferrin to TfR, consistent with our demonstration that HFE, transferrin, and TfR form a ternary complex.

Selected figure(s)

Figure 1.
Figure 1. Crystal Structure of HFE and Comparison to a Class I MHC Molecule(A) Ribbon diagram shows that HFE resembles class I molecules in the fold of the heavy chain (blue) and in its association with the β2m light chain (green). Cys-260, the residue substituted in the Cys260Tyr mutation, disulfide bonds with Cys-203.(B) Ribbon drawing of a top view of the HFE α1-α2 platform. His-41 (red), the site of the His41Asp mutation, interacts with Asp-73 (green).(C) The HFE model in the region of the Cys-260—Cys-203 disulfide bond is shown superimposed on a 2F[o]−F[c] annealed omit electron density map ([21]) contoured at 1σ. The average B factor for the residues shown is 48 Å^2.(D) Close-up of a histidine cluster and nearby tyrosine located underneath the right-hand side of the platform. His-94 is found in class I MHC molecules (class I His-93); His-89 and His-123 are present only in human ([16]), rat (EMBL accession number AJ001517), and mouse ( [20]) HFE. His-87 is present in human, but not mouse or rat, HFE.(A), (B), and (D) were made with Molscript ([28]) and rendered with Raster3D ( [34]). (C) was prepared with O ( [23]).

Figure 2.
Figure 2. The Counterpart of the Class I Peptide-Binding Groove is Narrowed in HFE by Translation of the α1 Helix(A) Cα stereo superpositions based on Cα atoms in the platform β strands of HFE with class I and class I–related proteins. Top, HLA-A2 (green, including a ball-and-stick representation of bound peptide; PDB code 2CLR) and HFE (magenta). Heavy chains share 37% amino acid sequence identity. Middle, Rat FcRn (green; PDB code 1FRU) and HFE (magenta). Heavy chains share 28% sequence identity. HFE Pro-166 (labeled) is analogous to FcRn Pro-162, located at a kink in the FcRn α2 helix. Bottom, Mouse CD1 (green) ([50]) and HFE (magenta). Heavy chains share 22% sequence identity. HFE Pro-166 (labeled) is analogous to CD1 Pro-162, located at a kink in the CD1 α2 helix.(B) Peptide-binding groove of HLA-A2 with labeled binding pockets.(C) HFE counterpart of the class I binding groove showing residues that would clash with a bound peptide. HFE side chains shown in white (same in HFE and HLA-A2) and green (different in HFE and HLA-A2) have at least two steric clashes with polyalanine versions of four different nonameric peptides (from HLA-A2 structures, PDB codes 1HHG, 1HHI, 1HHJ, and 1HHK; [30]) that were superimposed upon HFE after alignment of HLA-A2 and HFE. Steric clashes are defined as occurring when atoms are closer than the sum of their van der Waals radii minus 0.4 Å. The blue side chain would clash with peptides containing side chains larger than alanine.All panels were made with Molscript ([28]) and rendered with Raster3D ( [34]).

The above figures are reprinted by permission from Cell Press: Cell (1998, 93, 111-123) copyright 1998.

Figures were selected by an automated process.