PDBsum entry: 1rj8

Hormone/growth factor

PDB id: 1rj8

Contents

Protein chains

(+ 0 more) 140 a.a. *

Waters ×182

* Residue conservation analysis

PDB id:

1rj8

Name:

Hormone/growth factor

Title:

The crystal structure of tnf family member eda-a2

Structure:

Ectodysplasin-a isoform eda-a2. Chain: a, b, d, e, f, g. Fragment: tnf domain of eda-a2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Strain: pcc 7942. Gene: eda gene, splice form eda-a2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Trimer (from PQS)

Resolution:

2.23Å R-factor: 0.204 R-free: 0.241

Authors:

S.G.Hymowitz,D.M.Compaan,M.Yan,H.Ackerly,V.M.Dixit,M.A.Staro A.M.De Vos

Key ref:

S.G.Hymowitz et al. (2003). The crystal structures of EDA-A1 and EDA-A2: splice variants with distinct receptor specificity. Structure, 11, 1513-1520. PubMed id: 14656435 DOI: 10.1016/j.str.2003.11.009

Date:

18-Nov-03 Release date: 09-Dec-03

Protein chains

Q92838  (EDA_HUMAN) -  Ectodysplasin-A

Seq: 391 a.a.

Struc: 140 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: membrane (1 term)
• Biological process: immune response (1 term)
• Biochemical function: protein binding (2 terms)

DOI no: 10.1016/j.str.2003.11.009

Structure 11:1513-1520 (2003)

PubMed id: 14656435

The crystal structures of EDA-A1 and EDA-A2: splice variants with distinct receptor specificity.

S.G.Hymowitz, D.M.Compaan, M.Yan, H.J.Wallweber, V.M.Dixit, M.A.Starovasnik, A.M.de Vos.

ABSTRACT

EDA is a tumor necrosis factor family member involved in ectodermal development. Splice variants EDA-A1 and EDA-A2 differ only by the presence of Glu 308 and Val 309 in the expected receptor binding region of EDA-A1 but not EDA-A2. This two amino acid difference functions as a switch controlling receptor specificity. EDA-A1 binds only to EDAR, while EDA-A2 is specific for XEDAR. In order to understand the structural basis of this switch, we determined the X-ray crystal structures of the TNF domain of both EDA-A1 and EDA-A2 at 2.3 A and 2.2 A, respectively. While the backbone conformation around the splice difference is similar in both isoforms, the conformation of the following loop, the surface charge, and the shape of the expected receptor binding site differ significantly.

Selected figure(s)

Figure 2.
Figure 2. Electrostatic Surface of EDA-A1 (Left) and EDA-A2 (Right) and the Predicted Receptor Binding SiteThe molecular surface of both EDA isoforms is colored according to the calculated electrostatic surface potential with +5 kT in blue, neutral in white, and -5 kT in red. The predicted receptor binding surface is outlined in yellow. The subdomain structure of XEDAR and EDAR is depicted schematically with the relative location and number of disulfide bonds indicated by yellow lines. The N termini of the receptors are at the top of the figure. CRDs are labeled.

The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 1513-1520) copyright 2003.

Figure was selected by an automated process.