PDBsum entry: 1rf3

Signaling protein

PDB id: 1rf3

Contents

Protein chains

192 a.a. *

24 a.a. *

* Residue conservation analysis

PDB id:

1rf3

Name:

Signaling protein

Title:

Structurally distinct recognition motifs in lymphotoxin-b receptor and cd40 for traf-mediated signaling

Structure:

Tnf receptor associated factor 3. Chain: a. Fragment: recognition motif (residues 377-568). Synonym: cd40 receptor associated factor 1, craf1, cd40 binding protein, cd40bp, lmp1 associated protein, lap1, cap-1. Engineered: yes. 24-residue peptide from lymphotoxin-b receptor. Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: traf3 or craf1 or cap1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: the peptide was chemically synthesized, the sequence of the peptide occurs naturally in humans (homo

Biol. unit:

Tetramer (from PDB file)

Resolution:

3.50Å R-factor: 0.266 R-free: 0.315

Authors:

C.Li,P.S.Norris,C.Z.Ni,M.L.Havert,E.M.Chiong,B.R.Tran, E.Cabezas,G.Cheng,J.C.Reed,A.C.Satterthwait,C.F.Ware,K.R.El

Key ref:

C.Li et al. (2003). Structurally distinct recognition motifs in lymphotoxin-beta receptor and CD40 for tumor necrosis factor receptor-associated factor (TRAF)-mediated signaling. J Biol Chem, 278, 50523-50529. PubMed id: 14517219 DOI: 10.1074/jbc.M309381200

Date:

07-Nov-03 Release date: 06-Jul-04

Protein chain

Q13114  (TRAF3_HUMAN) -  TNF receptor-associated factor 3

Seq: 568 a.a.

Struc: 192 a.a.

Protein chain

P36941  (TNR3_HUMAN) -  Tumor necrosis factor receptor superfamily member 3

Seq: 435 a.a.

Struc: 24 a.a.

DOI no: 10.1074/jbc.M309381200

J Biol Chem 278:50523-50529 (2003)

PubMed id: 14517219

Structurally distinct recognition motifs in lymphotoxin-beta receptor and CD40 for tumor necrosis factor receptor-associated factor (TRAF)-mediated signaling.

C.Li, P.S.Norris, C.Z.Ni, M.L.Havert, E.M.Chiong, B.R.Tran, E.Cabezas, J.C.Reed, A.C.Satterthwait, C.F.Ware, K.R.Ely.

ABSTRACT

Lymphotoxin-beta receptor (LTbetaR) and CD40 are members of the tumor necrosis factor family of signaling receptors that regulate cell survival or death through activation of NF-kappaB. These receptors transmit signals through downstream adaptor proteins called tumor necrosis factor receptor-associated factors (TRAFs). In this study, the crystal structure of a region of the cytoplasmic domain of LTbetaR bound to TRAF3 has revealed an unexpected new recognition motif, 388IPEEGD393, for TRAF3 binding. Although this motif is distinct in sequence and structure from the PVQET motif in CD40 and PIQCT in the regulator TRAF-associated NF-kappaB activator (TANK), recognition is mediated in the same binding crevice on the surface of TRAF3. The results reveal structurally adaptive "hot spots" in the TRAF3-binding crevice that promote molecular interactions driving specific signaling after contact with LTbetaR, CD40, or the downstream regulator TANK.

Selected figure(s)

Figure 1.
FIG. 1. Structure of the LT R/TRAF3 complex. Schematic representation of the TRAF3 trimer is shown as a ribbon diagram with each subunit colored separately. The three subunits are stabilized by coiled-coil interactions between the elongated N-terminal helices of each subunit. Each subunit binds one LT R molecule, which is represented as a ball-and-stick model. LT R binds to a crevice at the edge of the TRAF3 -sandwich domain. In this view, the cell membrane is located at the top of the image.

Figure 4.
FIG. 4. LT R/TRAF3 recognition. Close-up view of the molecular contacts between the recognition motif of LT R (ball-and-stick model) bound to the crevice at the edge of TRAF3 (ribbon model) is shown. This set of interactions is identical for each TRAF3 subunit in the trimer. Critical contact residues are labeled, and the labels for TRAF3 residues are underlined. The hydrogen bonds are indicated as dotted lines.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 50523-50529) copyright 2003.

Figures were selected by the author.