PDBsum entry 3di2

Cytokine/cytokine receptor

PDB id: 3di2

Contents

Protein chains

115 a.a. *

195 a.a. *

Ligands

1PE

Waters ×28

* Residue conservation analysis

PDB id:

3di2

Name:

Cytokine/cytokine receptor

Title:

Crystal structure of the complex of human interleukin-7 with unglycosylated human interleukin-7 receptor alpha ectodomain

Structure:

Interleukin-7. Chain: a, c. Fragment: unp residues 26 to 177. Synonym: il-7. Engineered: yes. Mutation: yes. Interleukin-7 receptor subunit alpha. Chain: b, d. Fragment: unp residues 21 to 239 (ligand binding ectodomain).

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: il7. Expressed in: escherichia coli. Gene: il7r.

Resolution:

2.70Å R-factor: 0.212 R-free: 0.267

Authors:

C.A.Mcelroy,J.A.Dohm,S.T.R.Walsh

Key ref:

C.A.McElroy et al. (2009). Structural and Biophysical Studies of the Human IL-7/IL-7Ralpha Complex. Structure, 17, 54-65. PubMed id: 19141282 DOI: 10.1016/j.str.2008.10.019

Date:

19-Jun-08 Release date: 27-Jan-09

Protein chains

P13232  (IL7_HUMAN) -  Interleukin-7 from Homo sapiens

Seq: 177 a.a.

Struc: 115 a.a.

Protein chains

P16871  (IL7RA_HUMAN) -  Interleukin-7 receptor subunit alpha from Homo sapiens

Seq: 459 a.a.

Struc: 195 a.a.*

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

DOI no: 10.1016/j.str.2008.10.019

Structure 17:54-65 (2009)

PubMed id: 19141282

Structural and Biophysical Studies of the Human IL-7/IL-7Ralpha Complex.

C.A.McElroy, J.A.Dohm, S.T.Walsh.

ABSTRACT

IL-7 and IL-7Ralpha bind the gamma(c) receptor, forming a complex crucial to several signaling cascades leading to the development and homeostasis of T and B cells. We report that the IL-7Ralpha ectodomain uses glycosylation to modulate its binding constants to IL-7, unlike the other receptors in the gamma(c) family. IL-7 binds glycosylated IL-7Ralpha 300-fold more tightly than unglycosylated IL-7Ralpha, and the enhanced affinity is attributed primarily to an accelerated on rate. Structural comparison of IL-7 in complex to both forms of IL-7Ralpha reveals that glycosylation does not participate directly in the binding interface. The SCID mutations of IL-7Ralpha locate outside the binding interface with IL-7, suggesting that the expressed mutations cause protein folding defects in IL-7Ralpha. The IL-7/IL-7Ralpha structures provide a window into the molecular recognition events of the IL-7 signaling cascade and provide sites to target for designing new therapeutics to treat IL-7-related diseases.

Selected figure(s)

Figure 1.
Figure 1. Binding Kinetic Sensorgrams for the IL-7/IL-7Rα Interaction Determined Using SPR
(A) Binding kinetics between unglycosylated IL-7 and IL-7Rα, both from E. coli (EC).
(B and C) Binding kinetics of IL-7 (EC) to glycosylated IL-7Rα from Chinese hamster ovary (CHO) and Schneider (S2) insect cells, respectively.
(D) Binding kinetics of IL-7 to PNGase F-treated IL-7Rα (S2).
(E) Binding kinetics between IL-7 (EC) and Endo H-treated IL-7Rα (S2).
The binding kinetics sensorgrams are in black. The red curves are global fits of the SPR data to a two-step binding reaction model to determine the binding kinetics.

Figure 3.
Figure 3. Structural Comparison between Unglycosylated and Glycosylated IL-7/IL-7Rα Complexes
(A) Superimposition of the unglycosylated structures (wheat and blue) onto the glycosylated structure (green) using the D1 and D2 domains of the receptors.
(B) Molecular surface view of IL-7 and IL-7Rα highlighting the hydrophobic (orange) and hydrophilic (lime green) residues in the binding interface.
(C and D) Bar graphs showing the amount of buried surface area for IL-7 (C) and IL-7Rα (D) in the unglycosylated (red bars) and glycosylated (blue bars) complexes. Secondary structure locations are labeled below the residues.
(E) Two views of the intermolecular interactions observed between the IL-7/IL-7Rα unglycosylated (wheat) and glycosylated (green) structures. H bonds are depicted as dashes colored black and green for the unglycosylated and glycosylated complexes, respectively.

The above figures are reprinted from an Open Access publication published by Cell Press: Structure (2009, 17, 54-65) copyright 2009.

Figures were selected by the author.