PDBsum entry: 1aly

Cytokine

PDB id: 1aly

Contents

Protein chain

146 a.a. *

Waters ×192

* Residue conservation analysis

PDB id:

1aly

Name:

Cytokine

Title:

Crystal structure of human cd40 ligand

Structure:

Cd40 ligand. Chain: a. Fragment: extracellular domain fragment. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: pichia pastoris. Tissue: blood. Cell: t-lymphocyte. Cellular_location: membrane. Expressed in: pichia pastoris. Expression_system_taxid: 4922

Biol. unit:

Homo-Trimer (from PDB file)

Resolution:

2.00Å R-factor: 0.223 R-free: 0.295

Authors:

M.Karpusas,Y.M.Hsu,D.Thomas

Key ref:

M.Karpusas et al. (1995). 2 A crystal structure of an extracellular fragment of human CD40 ligand. Structure, 3, 1031-1039. PubMed id: 8589998 DOI: 10.1016/S0969-2126(01)00239-8

Date:

05-Jun-97 Release date: 17-Sep-97

Protein chain

P29965  (CD40L_HUMAN) -  CD40 ligand

Seq: 261 a.a.

Struc: 146 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: membrane (1 term)
• Biological process: immune response (1 term)
• Biochemical function: tumor necrosis factor receptor binding (1 term)

DOI no: 10.1016/S0969-2126(01)00239-8

Structure 3:1031-1039 (1995)

PubMed id: 8589998

2 A crystal structure of an extracellular fragment of human CD40 ligand.

M.Karpusas, Y.M.Hsu, J.H.Wang, J.Thompson, S.Lederman, L.Chess, D.Thomas.

ABSTRACT

BACKGROUND: The CD40 ligand (CD40L) is a member of the tumor necrosis factor (TNF) family of proteins and is transiently expressed on the surface of activated T cells. The binding of CD40L to CD40, which is expressed on the surface of B cells, provides a critical and unique pathway of cellular activation resulting in antibody isotype switching, regulation of apoptosis, and B cell proliferation and differentiation. Naturally occurring mutations of CD40L result in the clinical hyper-IgM syndrome, characterized by an inability to produce immunoglobulins of the IgG, IgA and IgE isotypes. RESULTS: We have determined the crystal structure of a soluble extracellular fragment of human CD40L to 2 A resolution and with an R factor of 21.8%. Although the molecule forms a trimer similar to that found for other members of the TNF family, such as TNF alpha and lymphotoxin-alpha, and exhibits a similar overall fold, there are considerable differences in several loops including those predicted to be involved in CD40 binding. CONCLUSIONS: The structure suggests that most of the hyper-IgM syndrome mutations affect the folding and stability of the molecule rather than the CD40-binding site directly. Despite the fact that the hyper-IgM syndrome mutations are dispersed in the primary sequence, a large fraction of them are clustered in space in the vicinity of a surface loop, close to the predicted CD40-binding site.

Selected figure(s)

Figure 1.
Figure 1. Representative regions of the final 2F[o]–F[c] electron density map contoured at 2.5σ. (a) Residues in the vicinity of the CD40 binding site. (b) View of a cluster of three tyrosine and three histidine residues formed in the vicinity of the center of the trimer. The threefold axis is vertical. Figure 1. Representative regions of the final 2F[o]–F[c] electron density map contoured at 2.5σ. (a) Residues in the vicinity of the CD40 binding site. (b) View of a cluster of three tyrosine and three histidine residues formed in the vicinity of the center of the trimer. The threefold axis is vertical.

Figure 3.
Figure 3. Stereo diagram of superimposed Cα backbones of TNFα (green), LTα (blue) and CD40L (red) crystal structures. The view is approximately the same as in Figure 2. Figure 3. Stereo diagram of superimposed Cα backbones of TNFα (green), LTα (blue) and CD40L (red) crystal structures. The view is approximately the same as in [3]Figure 2.

The above figures are reprinted by permission from Cell Press: Structure (1995, 3, 1031-1039) copyright 1995.

Figures were selected by an automated process.