Amino acid residues required for binding of lymphocyte function-associated antigen 3 (CD58) to its counter-receptor CD2.

Osborn, Laurelee; Day, Eric S.; Miller, Glenn T.; Karpusas, Michael; Tizard, Richard; Meuer, Stefan; Hochman, Paula S.

doi:10.1084/jem.181.1.429

Cited by 15 publications

(14 citation statements)

References 26 publications

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“…Prior studies have shown that the N-terminal membrane distaldomain (D1) mediates the adhesion function of the molecule by binding to the relevant counterreceptor (Sayre et al, 1989;Recny et al, 1990). Mutational analysis of human CD2 has demonstrated that the CD58 binding surface is located on the highly charged GFCC'C" face of the protein (Peterson & Seed, 1987;Arulanandam et al, 1993b;Somoza et al, 1993;Osborn et al, 1995). Notably, this same surface area forms a homodimeric contact in the crystal structures of rat and human CD2 (Jones et al, 1992;Bodian et al, 1994).…”

Section: Introductionmentioning

confidence: 93%

Ligand-induced Conformational Change Within the CD2 Ectodomain Accompanies Receptor Clustering: Implication for Molecular Lattice Formation

Smolyar

Sunder‐Plaßmann

et al. 1996

Journal of Molecular Biology

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Section: Introductionmentioning

confidence: 93%

Ligand-induced Conformational Change Within the CD2 Ectodomain Accompanies Receptor Clustering: Implication for Molecular Lattice Formation

Smolyar

Sunder‐Plaßmann

et al. 1996

Journal of Molecular Biology

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“…The inclusion of K87 in the interface only requires slight adjustment of the sCD2 lattice model, as noted (25), and the sidechain of K30 lies beneath the CCЈ loop, where it could affect CD2 binding indirectly. Thus, only D84, for which the mutagenesis data are, in any case, discordant (25,26), lies well outside the region of contact and seems unlikely to have a role in binding.…”

Section: Expression and Functional Analysis Of A Crystallizablementioning

confidence: 99%

“…On docking the CD2 and CD58 V-set domains in an orientation based on homodimeric, orthogonal lattice contacts observed in crystals of human sCD2 (Fig. 5A), all but three (K30, K87, and D84) of the residues implicated in the mutational analyses of CD58 (25,26) can, by selecting alternative sidechain rotamer conformations, be brought within binding- Fig. 3 A and B, respectively.…”

Section: Expression and Functional Analysis Of A Crystallizablementioning

confidence: 99%

Crystal structure of the CD2-binding domain of CD58 (lymphocyte function-associated antigen 3) at 1.8-Å resolution

Ikemizu

Sparks

Merwe

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

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The binding of the cell surface molecule CD58 (formerly lymphocyte function-associated antigen 3) to its ligand, CD2, significantly increases the sensitivity of antigen recognition by T cells. This was the first heterophilic cell adhesion interaction to be discovered and is now an important paradigm for analyzing the structural basis of cell-cell recognition. The crystal structure of a CD2-binding chimeric form of CD58, solved to 1.8-Å resolution, reveals that the ligand binding domain of CD58 has the expected Ig superfamily V-set topology and shares several of the hitherto unique structural features of CD2, consistent with previous speculation that the genes encoding these molecules arose via duplication of a common precursor. Nevertheless, evidence for considerable divergence of CD2 and CD58 is also implicit in the structures. Mutations that disrupt CD2 binding map to the highly acidic surface of the AGFCCC ␤-sheet of CD58, which, unexpectedly, lacks marked shape complementarity to the equivalent, rather more basic CD58-binding face of human CD2. The specificity of the very weak interactions of proteins mediating cell-cell recognition may often derive largely from electrostatic complementarity, with shape matching at the protein-protein interface being less exact than for interactions that combine specificity with high affinity, such as those involving antibodies.Antibodies to CD2 and CD58 (lymphocyte function-associated antigen 3) were among the first found to block the functions of human T lymphocytes in in vitro assays (reviewed in ref. 1). The cognate ligand-receptor relationship of CD2 and CD58, the first heterophilic protein interaction to be identified at the cell surface, was directly established when purified CD2 was shown to bind to cellular CD58 (2). CD58 is expressed in both haemopoietic and nonhaemopoietic lineages, including the endothelium (3). The binding of CD2 to CD58 is known to significantly enhance the efficiency of antigen recognition in vitro (4), and studies of CD2-deficient mice indicate that the interaction of CD2 with the murine ligand CD48 influences both positive selection and T cell activation (5).The sequencing of cDNAs encoding CD58 revealed that, like CD2, the extracellular region of CD58 consists of single V-set and C2-set Ig superfamily (IgSF) domains (reviewed in ref. 6). Along with CD48 and several other molecules, CD2 and CD58 belong to a subset of the IgSF that is likely to have arisen via the duplication of an ancestral gene encoding a homophilic cell-cell recognition molecule (6).Studies of the interaction of CD2 with its ligands have been informative with respect to the mechanism(s) of proteinprotein recognition at the cell surface (reviewed in ref. 7). The crystal structures of soluble forms of rat (8) and human (9) CD2 [soluble CD2 (sCD2)] provided the initial views of the complete extracellular regions of cell adhesion molecules. This work drew attention to charged residues clustered at the ligand binding site of CD2 and to the unusual flatness of the bindin...

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“…Based on the solved structures of the adhesion domain of human CD2 (1dCD2) (Wyss et al ., 1995), a molecular model of wild‐type 1dCD58 has been constructed (Arulanandam et al ., 1994). The results of alanine scanning (Arulanandam et al ., 1994; Osborn et al ., 1995) suggest that the CD2‐binding epitope on CD58 can be mapped to the GFCC′C″ face analogous to the CD58‐binding site of CD2 (Arulanandam et al ., 1993b; Somoza et al ., 1993). Accordingly, five surface‐exposed hydrophobic residues that are not involved in the binding function initially were identified from a total of 33 hydrophobic residues (excluding proline and glycine) in 1dCD58 (Figure 2A).…”

Section: Resultsmentioning

confidence: 99%

“…Although structural details of the human CD2 adhesion domain have been available through both NMR and X‐ray crystallography studies (Withka et al ., 1993; Bodian et al ., 1994; Wyss et al ., 1995), modeling of the CD2–CD58 interaction has been hindered by the lack of structural knowledge about the CD58 adhesion domain. The overall fold of the CD58 adhesion domain was predicted to be an immunoglobulin variable domain fold, and the ligand‐binding site was mapped to the GFCC′C″ face, similar to the adhesion domain of CD2 according to mutagenesis studies (Arulanandam et al ., 1994; Osborn et al ., 1995). However, the details about the amino acid residues involved in binding still await the experimental determination of the CD58 structure.…”

Section: Introductionmentioning

confidence: 99%

Functional glycan-free adhesion domain of human cell surface receptor CD58: design, production and NMR studies

et al. 1999

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A general strategy is presented here for producing glycan-free forms of glycoproteins without loss of function by employing apolar-to-polar mutations of surface residues in functionally irrelevant epitopes. The success of this structure-based approach was demonstrated through the expression in Escherichia coli of a soluble 11 kDa adhesion domain extracted from the heavily glycosylated 55 kDa human CD58 ectodomain. The solution structure was subsequently determined and binding to its counter-receptor CD2 studied by NMR. This mutant adhesion domain is functional as determined by several experimental methods, and the size of its binding site has been probed by chemical shift perturbations in NMR titration experiments. The new structural information supports a 'hand-shake' model of CD2-CD58 interaction involving the GFCCЈCЈЈ faces of both CD2 and CD58 adhesion domains. The region responsible for binding specificity is most likely localized on the C, CЈ and CЈЈ strands and the C-CЈ and CЈ-CЈЈ loops on CD58.

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Amino acid residues required for binding of lymphocyte function-associated antigen 3 (CD58) to its counter-receptor CD2.

Cited by 15 publications

References 26 publications

Ligand-induced Conformational Change Within the CD2 Ectodomain Accompanies Receptor Clustering: Implication for Molecular Lattice Formation

Ligand-induced Conformational Change Within the CD2 Ectodomain Accompanies Receptor Clustering: Implication for Molecular Lattice Formation

Crystal structure of the CD2-binding domain of CD58 (lymphocyte function-associated antigen 3) at 1.8-Å resolution

Functional glycan-free adhesion domain of human cell surface receptor CD58: design, production and NMR studies

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