PDBsum entry 2pkd

Signaling protein

PDB id: 2pkd

Contents

Protein chain

(+ 0 more) 107 a.a. *

Metals

_CL ×2

Waters ×393

* Residue conservation analysis

PDB id:

2pkd

Name:

Signaling protein

Title:

Crystal structure of cd84: insite into slam family function

Structure:

Slam family member 5. Chain: a, b, c, d, e, f. Fragment: cd84. Synonym: signaling lymphocytic activation molecule 5, leukocyte differentiation antigen cd84, cd84 antigen, cell surface antigen max.3, hly9-beta. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cd84, slamf5. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.04Å R-factor: 0.201 R-free: 0.277

Authors:

Q.Yan,V.N.Malashkevich,A.Fedorov,E.Cao,J.W.Lary,J.L.Cole, S.G.Nathenson,S.C.Almo

Key ref:

Q.Yan et al. (2007). Structure of CD84 provides insight into SLAM family function. Proc Natl Acad Sci U S A, 104, 10583-10588. PubMed id: 17563375 DOI: 10.1073/pnas.0703893104

Date:

17-Apr-07 Release date: 26-Jun-07

Protein chains

Q9UIB8  (SLAF5_HUMAN) -  SLAM family member 5 from Homo sapiens

Seq: 345 a.a.

Struc: 107 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1073/pnas.0703893104

Proc Natl Acad Sci U S A 104:10583-10588 (2007)

PubMed id: 17563375

Structure of CD84 provides insight into SLAM family function.

Q.Yan, V.N.Malashkevich, A.Fedorov, E.Fedorov, E.Cao, J.W.Lary, J.L.Cole, S.G.Nathenson, S.C.Almo.

ABSTRACT

The signaling lymphocyte activation molecule (SLAM) family includes homophilic and heterophilic receptors that modulate both adaptive and innate immune responses. These receptors share a common ectodomain organization: a membrane-proximal immunoglobulin constant domain and a membrane-distal immunoglobulin variable domain that is responsible for ligand recognition. CD84 is a homophilic family member that enhances IFN-gamma secretion in activated T cells. Our solution studies revealed that CD84 strongly self-associates with a K(d) in the submicromolar range. These data, in combination with previous reports, demonstrate that the SLAM family homophilic affinities span at least three orders of magnitude and suggest that differences in the affinities may contribute to the distinct signaling behavior exhibited by the individual family members. The 2.0 A crystal structure of the human CD84 immunoglobulin variable domain revealed an orthogonal homophilic dimer with high similarity to the recently reported homophilic dimer of the SLAM family member NTB-A. Structural and chemical differences in the homophilic interfaces provide a mechanism to prevent the formation of undesired heterodimers among the SLAM family homophilic receptors. These structural data also suggest that, like NTB-A, all SLAM family homophilic dimers adopt a highly kinked organization spanning an end-to-end distance of approximately 140 A. This common molecular dimension provides an opportunity for all two-domain SLAM family receptors to colocalize within the immunological synapse and bridge the T cell and antigen-presenting cell.

Selected figure(s)

Figure 1.
Fig. 1. Oligomeric state of CD84 and CD84-T99A mutation. Overlay of the normalized g(s*) plots from DcDt+ analysis of the sedimentation velocity data at different concentrations: CD84 IgV domain (A), CD84 IgVC domain (B), and CD84-T99A (C).

Figure 4.
Fig. 4. Model of human CD84 involved in T cell activation. The ribbon diagram representation of the model of the CD84 homophilic interaction, NTB-A homophilic interaction, and CD2–CD58 heterophilic interaction between T cell and APC. The MHC–TCR complex is also shown for a comparison of molecular dimensions.

Figures were selected by an automated process.