PDBsum entry 1j87

Immune system

PDB id

1j87

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Contents

			Protein chain

					168 a.a. *

			Ligands

					NAG-NAG ×2


					NAG-NAG-BMA-MAN- MAN


					NAG-NAG-FUC

* Residue conservation analysis

PDB id:

1j87

Links

Name:

Immune system

Title:

Human high affinity fc receptor fc(epsilon)ri(alpha), hexagonal crystal form 1

Structure:

High affinity immunoglobulin epsilon receptor alpha- subunit. Chain: a. Fragment: extracellular fragment. Synonym: fc(epsilon)ri(alpha). Ige fc receptor, alpha-subunit. Fc- epsilon ri-alpha. Engineered: yes. Mutation: yes. Other_details: glycosylated protein

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

3.20Å

R-factor:

0.264

R-free:

0.306

Authors:

S.C.Garman,S.Sechi,J.P.Kinet,T.S.Jardetzky

Key ref:

S.C.Garman et al. (2001). The analysis of the human high affinity IgE receptor Fc epsilon Ri alpha from multiple crystal forms. J Mol Biol, 311, 1049-1062. PubMed id: 11531339 DOI: 10.1006/jmbi.2001.4929

Date:

20-May-01

Release date:

29-Aug-01

PROCHECK

	Headers

	References

Protein chain

P12319 (FCERA_HUMAN) - High affinity immunoglobulin epsilon receptor subunit alpha from Homo sapiens

Seq: Struc:					257 a.a. 168 a.a.*

Key:

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1006/jmbi.2001.4929	J Mol Biol 311:1049-1062 (2001)
PubMed id: 11531339

The analysis of the human high affinity IgE receptor Fc epsilon Ri alpha from multiple crystal forms.
S.C.Garman, S.Sechi, J.P.Kinet, T.S.Jardetzky.

ABSTRACT

We have solved the structure of the human high affinity IgE receptor, Fc epsilon RI alpha, in six different crystal forms, showing the structure in 15 different chemical environments. This database of structures shows no change in the overall shape of the molecule, as the angle between domains 1 and 2 (D1 and D2) varies little across the ensemble. However, the receptor has local conformational variability in the C' strand of D2 and in the BC loop of D1. In every crystal form, a residue inserts between tryptophan residues 87 and 110, mimicking the position of a proline from the IgE ligand. The different crystal forms reveal a distribution of carbohydrates lining the front and back surfaces of the structure. An analysis of crystal contacts in the different forms indicates regions where the molecule interacts with other proteins, and reveals a potential new binding site distal to the IgE binding site. The results of this study point to new directions for the design of molecules to inhibit the interaction of Fc epsilon RI alpha with its natural ligand and thus to prevent a primary step in the allergic response.

Selected figure(s)



	Figure 2. Figure 2. Close-up of binding site 1 in eight different structures. C^a positions for residues 125-138 are shown, along with side-chain atoms for residues Tyr129, Trp130, and Tyr131. (a) Chains are colored according to the scheme in Figure 1: form M1, white; form M2 (copy A), green; form M2 (copy B), yellow; form H1, blue; form Complex1, cyan; form T1 (copies A and B), red; form T2 (copy A), magenta. Other copies of the tetragonal forms are identical; only one representative structure is shown. In form M1, form M2A, and form H1, the coordinates differ from canonical C' structure. (b) The same Figure is shown with a different coloring scheme, showing the variation in location of three aromatic residues. Side-chain atoms for Tyr129 appear red, for Trp130 appear blue, and for Tyr131 appear yellow. Tyr131 in form M2A falls in nearly the same location as Tyr129 in most crystal forms.		Figure 3. Figure 3. Electron density from four structures. Electron density maps were calculated using s[a]-weighted simulated annealing composite omit map protocols in the program CNS. Atoms are drawn from residue 125 to 134, near binding site 1 in domain D2, and the maps are drawn around the atoms. (a) Form M1. The 2.4 Å map is contoured at 1.2s. The strand is in a location intermediate between C' and D strands. (b) Form M2, copy A. The 3.2 Å map is contoured at 1.2s. The atoms form a single turn of a-helix surrounded by random coil and are in found in an intermediate location between C' and D strands. (c) Form H1. The 3.2 Å map is contoured at 0.9s. The atoms have crossed over to the opposite sheet of the Ig domain; they form b strand D hydrogen-bonded to the E strand. (d) Form M2, copy B. The 3.2 Å map is contoured at 1.2s. This is the most common conformation for the Fc epsilon RIa chain, a C' strand hydrogen-bonded to the C strand in D2, seen in 12 of the 15 structures.

Figures were selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21516097

M.D.Holdom, A.M.Davies, J.E.Nettleship, S.C.Bagby, B.Dhaliwal, E.Girardi, J.Hunt, H.J.Gould, A.J.Beavil, J.M.McDonnell, R.J.Owens, and B.J.Sutton (2011).
Conformational changes in IgE contribute to its uniquely slow dissociation rate from receptor FcɛRI.

Nat Struct Mol Biol, 18, 571-576.

PDB codes:

2wqr 2y7q

20039648

A.Ross, D.C.Soares, D.Covelli, C.Pannecouque, L.Budd, A.Collins, N.Robertson, S.Parsons, E.De Clercq, P.Kennepohl, and P.J.Sadler (2010).
Oxovanadium(IV) cyclam and bicyclam complexes: potential CXCR4 receptor antagonists.

Inorg Chem, 49, 1122-1132.

18301424

H.J.Gould, and B.J.Sutton (2008).
IgE in allergy and asthma today.

Nat Rev Immunol, 8, 205-217.

18703499

J.Hunt, M.G.Bracher, J.Shi, S.Fleury, D.Dombrowicz, H.J.Gould, B.J.Sutton, and A.J.Beavil (2008).
Attenuation of IgE affinity for FcepsilonRI radically reduces the allergic response in vitro and in vivo.

J Biol Chem, 283, 29882-29887.

17828717

C.Peters, M.Bacher, C.L.Buenemann, F.Kricek, J.M.Rondeau, and K.Weigand (2007).
Conformationally constrained mimics of the membrane-proximal domain of Fc epsilonRIalpha.

Chembiochem, 8, 1785-1789.

16014522

D.Macglashan (2005).
IgE and Fc{epsilon}RI regulation.

Ann N Y Acad Sci, 1050, 73-88.

15701702

T.M.Hunter, I.W.McNae, X.Liang, J.Bella, S.Parsons, M.D.Walkinshaw, and P.J.Sadler (2005).
Protein recognition of macrocycles: binding of anti-HIV metallocyclams to lysozyme.

Proc Natl Acad Sci U S A, 102, 2288-2292.

PDB codes:

1yik 1yil

15040582

J.M.Woof, and D.R.Burton (2004).
Human antibody-Fc receptor interactions illuminated by crystal structures.

Nat Rev Immunol, 4, 89-99.

14715661

N.Charles, R.C.Monteiro, and M.Benhamou (2004).
p28, a novel IgE receptor-associated protein, is a sensor of receptor occupation by its ligand in mast cells.

J Biol Chem, 279, 12312-12318.

12768205

A.B.Herr, E.R.Ballister, and P.J.Bjorkman (2003).
Insights into IgA-mediated immune responses from the crystal structures of human FcalphaRI and its complex with IgA1-Fc.

Nature, 423, 614-620.

PDB codes:

1ovz 1ow0

12500981

H.J.Gould, B.J.Sutton, A.J.Beavil, R.L.Beavil, N.McCloskey, H.A.Coker, D.Fear, and L.Smurthwaite (2003).
The biology of IGE and the basis of allergic disease.

Annu Rev Immunol, 21, 579-628.

12493733

S.C.Garman, W.N.Simcoke, A.W.Stowers, and D.N.Garboczi (2003).
Structure of the C-terminal domains of merozoite surface protein-1 from Plasmodium knowlesi reveals a novel histidine binding site.

J Biol Chem, 278, 7264-7269.

PDB code:

1n1i

11830661

G.R.Nakamura, M.E.Reynolds, Y.M.Chen, M.A.Starovasnik, and H.B.Lowman (2002).
Stable "zeta" peptides that act as potent antagonists of the high-affinity IgE receptor.

Proc Natl Acad Sci U S A, 99, 1303-1308.

PDB codes:

1kcn 1kco

12190931

H.Metzger (2002).
Molecular versatility of antibodies.

Immunol Rev, 185, 186-205.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.