PDBsum entry: 1d2q

Cytokine

PDB-id: 1d2q

Asymmetric unit

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PROCHECK

Protein chains

134 a.a. *

* Residue conservation analysis

Tools

Clefts Calculation

Biological unit*, trimer
(*as deduced by PQS)

PDB id:

1d2q

Name:

Cytokine

Title:

Crystal structure of human trail

Structure:

Tnf-related apoptosis inducing ligand. Chain: a, b. Fragment: extra cellular domain. Synonym: trail. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: bacteria. Expression_system_taxid: 2.

Biological unit:

Trimer (from PQS)

UniProt:

Chains A, B: P50591 (TNF10_HUMAN)

Seq:

Struc:

Seq:

281 a.a.

Struc:

134 a.a.

Key:	PfamA domain
Secondary structure	CATH domain

Resolution:

2.80Å

R-factor:

0.209

R-free:

0.282

Authors:

S.-S.Cha

Key ref:

S.S.Cha et al. (1999). 2.8 A resolution crystal structure of human TRAIL, a cytokine with selective antitumor activity.. Immunity, 11, 253-261. [PubMed id: 10485660] [DOI: 10.1016/S1074-7613(00)80100-4]

Date:

27-Sep-99

Release date:

11-Feb-00

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Surface

Key reference

DOI no: 10.1016/S1074-7613(00)80100-4

Immunity 11:253-261 (1999)

PubMed id: 10485660

2.8 A resolution crystal structure of human TRAIL, a cytokine with selective antitumor activity.

S.S.Cha, M.S.Kim, Y.H.Choi, B.J.Sung, N.K.Shin, H.C.Shin, Y.C.Sung, B.H.Oh.

ABSTRACT

TRAIL is a newly identified cytokine belonging to the large tumor necrosis factor (TNF) family. TRAIL is a novel molecule inducing apoptosis in a wide variety of tumor cells but not in normal cells. To help in elucidating its biological roles and designing mutants with improved therapeutic potential, we have determined the crystal structure of human TRAIL. The structure reveals that a unique frame insertion of 12-16 amino acids adopts a salient loop structure penetrating into the receptor-binding site. The loop drastically alters the common receptor-binding surface of the TNF family most likely for the specific recognition of cognate partners. A structure-based mutagenesis study demonstrates a critical role of the insertion loop in the cytotoxic activity of TRAIL.

Selected figure(s)

Figure 3.
Figure 3. The AA′′ Loop of TRAIL(A) Interactions of the AA′′ loop along the surface of TRAIL. The residues on the AA′′ and the GH loop are shown in green and khaki, respectively. The cyan dotted lines represent polar interactions. (B) The final 2F[o]-F[c] electron density map contoured at 1σ showing residues 145–155 on the AA′′ loop that interact with the outer β sheet platform. The orientation of the peptide segment is roughly perpendicular to that shown in (A) for clarity. The electron density of this external loop is weaker than that of the central β sheets.

Figure 5.
Figure 5. Sliced View of TRAILThe orientation of TRAIL is the same as in Figure 4. Cavities existing along the central 3-fold axis are in blue. Arrows 1 and 2 indicate the position of Cys-230 and Tyr-183, respectively. The cysteine residue from each subunit should be in the reduced form, since the TRAIL sample for the crystallization contained 1 mM dithiothreitol. The distance between the sulfur atoms (2.6 Å) and the molecular symmetry restriction indicate that these residues cannot form disulfide bonds even in an oxidizing condition. Figure 2 and Figure 3A were produced using the program MOLSCRIPT ( [12]), Figure 3B using the program O ( [16]), and Figure 4 and Figure 5 using the program GRASP ( [15]).

The above figures are reprinted by permission from Cell Press: Immunity (1999, 11, 253-261) copyright 1999.

Figures were selected by an automated process.