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PubMed1982

Interaction between 1,25-dihydroxyvitamin D3 receptors and intestinal nuclei. Binding to nuclear constituents in vitro.

The molecular action of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is thought to involve its localization within the nucleus of target cells, a process mediated by intracellular receptors. This report probes both the association between chick intestinal 1,25(OH)2D3 receptors and purified homologous nuclei and the interaction between this receptor and nucleic acids. 1,25(OH)2D3 receptors bound to purified nuclei in a apparently saturable manner (Kd = 2.2-4.8 X 10(-10) M) under conditions of intermediate ionic strength and constant protein concentration. Nuclear binding was hormone-dependent; whereas receptor-hormone complex (Rs) binds to nuclei under the ionic conditions employed here (greater than 70%), hormone-free (R0) receptors do not bind (less than 10%). Binding was localized to the nuclear chromatin fraction and was extremely sensitive to KCl concentration both in the incubation medium and during postincubation treatment of nuclei. The interaction appeared to be temperature-independent, suggesting the lack of a classic activation event characteristic of most steroid receptors. Partial digestion of intestinal nuclei with DNase I eliminated subsequent receptor binding by greater than 95%, pointing to the involvement of DNA in the binding interaction. In turn, receptors were found to bind to both DNA and RNA, a characteristic independent of receptor aggregation, but sensitive to disruption with increasing ionic strength buffers. Elution of both Rs and R0 from DNA appeared identical (0.28 M KCl), whereas the strength of interaction with RNA was much less (0.12 M KCl). Thus, while there appeared to be a fundamental difference between R0 and Rs, such that only the binding of receptor-hormone complex to nuclei was allowed under the conditions employed here, this characteristic was not observed during DNA binding. Nevertheless, the possibility exists that the in vivo interaction between 1,25(OH)2D3 receptor and nuclei involves DNA and that this nuclear constituent may be the ultimate site of action of this unique sterol hormone.

Animals↗
PubMed1992

Progesterone action through aggregation of a receptor on the sperm plasma membrane.

Rapid steroid effects, reported in several cell types, have pointed out the possibility of non-genomic mechanisms of action, presumably on cell surface receptors. Here we analyzed the effects of antibody-mediated aggregation of a novel type of progesterone receptor on the plasma membrane of human sperm cells. We report that aggregation of hormone-receptor complexes induces Ca2+ influx and a Ca(2+)-dependent exocytotic event in this system. These data suggest a possible mechanism for rapid steroid-induced events. Further research is warranted to examined if a similar mechanism is involved in rapid steroid effects in other cell types.

Biological Transport↗
PubMed1995

Protein tyrosine phosphatase activity associates with the high affinity IgE receptor and dephosphorylates the receptor subunits, but not Lyn or Syk.

Protein tyrosine phosphorylation is an early event in the high affinity IgE receptor (Fc epsilon RI)-mediated signaling cascade leading to secretion in mast cells. Numerous proteins, including the beta- and gamma-subunits of Fc epsilon RI, become tyrosine phosphorylated after receptor aggregation. Dephosphorylation of these proteins may be important to reverse and limit transmembrane signaling. RBL-2H3 mast cell lysates were found to contain protein tyrosine phosphatase activity that dephosphorylated the tyrosine-phosphorylated beta- and gamma-subunits of Fc epsilon RI. The protein tyrosine phosphatase activity associated with Fc epsilon RI and was equally present with receptors from nonactivated and stimulated cells. Moreover, the phosphatase eluted from the immunoprecipitates and, when added back, dephosphorylated both tyrosine-phosphorylated beta- and gamma-subunits, but not tyrosine-phosphorylated Lyn or Syk. These results strongly suggest that the IgE receptor-associated protein tyrosine phosphatase may regulate the steady state level of tyrosylphosphate of the beta- and gamma-subunits and, therefore, may modulate the interaction of these subunits with other downstream molecules, such as Syk.

Animals↗
PubMed2003

DNA-damaging reagents induce apoptosis through reactive oxygen species-dependent Fas aggregation.

DNA-damaging reagents may kill tumor cells through the generation of reactive oxygen species (ROS). Cytotoxic reagents may also induce apoptosis of cancer cells in Fas-FADD-dependent manners. In this study, we explored the possible link between these two apparently distinct pathways in T leukemia cell Jurkat. Our results demonstrated that gamma-irradiation, similar to cisplatin, induced apoptosis by triggering Fas aggregation and activating FADD-caspase-8 apoptotic cascade. The absence of caspase-8 or Fas greatly reduced the sensitivity to apoptosis mediated by DNA-damaging agents. In addition, apoptosis induced by cisplatin and gamma-irradiation, but not by Fas, was inhibited by ROS scavengers, including N-acetyl cysteine, MnTBAP, and C60. Importantly, these ROS scavengers effectively prevented the clustering of Fas receptor induced by cisplatin and gamma-irradiation. Our results suggest that cisplatin and gamma-irradiation promote ROS production, which in turn contributes to Fas receptor aggregation and cell death. The novel coupling between ROS and Fas clustering likely plays a significant role in apoptosis triggered by DNA-damaging reagents in Fas-expressing leukemia cells.

Adaptor Proteins, Signal Transducing↗
PubMed1988

Isolation and purification of an Fc epsilon receptor activated ion channel from the rat mast cell line RBL-2H3.

Derivatives of the antiallergic drug cromolyn [disodium 5,5'-[(2-hydroxy-1,3-propanediyl)-bis(oxy)]bis [4-oxo-(4H-1-benzopyran)-2- carboxylate]], which can be conjugated covalently at the propane 2-position to macromolecules and to insoluble matrices, were synthesized. Conjugates of these derivatives with macromolecules were examined for their binding to cells of the rat basophilic leukemia line RBL-2H3, which is widely employed as a model for immunologically induced mast cell degranulation. Only those drug-protein conjugates in which the cromolyn analogue with an amino group at the propane 2-carbon instead of the hydroxyl was linked to the carrier by glutaraldehyde were found to exhibit specific and saturable binding to these cells. Analysis of the binding data for these conjugates yielded an apparent binding constant of 3.8 +/- 0.2 X 10(8) M-1 and an apparent number of binding sites for the probe of 4000-8000 per cell. The conjugates found to bind specifically to the cells were also immobilized on agarose matrices and employed in an affinity-based isolation of the membrane component responsible for the observed binding. A single labeled polypeptide was eluted from these columns, onto which either whole cell lysates or solubilized purified plasma membranes of surface-radioiodinated RBL-2H3 cells had been adsorbed. This membrane protein appears on autoradiograms of nonreducing SDS-PAGE as a single broad band of approximately 110,000 daltons (Da) apparent molecular mass. On autoradiograms of reducing gels, the only band detected has an apparent mass of approximately 50,000 Da and appears narrower. Elution of the columns with the drug and disulfide-reducing agents or with the latter alone resulted in significantly higher yields of the 50-kDa polypeptide. Both the intact and reduced proteins bind strongly to immobilized concanavalin A and less so to immobilized wheat germ agglutinin, suggesting that the isolated intact protein is probably a dimer of two glycosylated subunits of similar molecular mass. Treatment of the reduced protein with endoglycosidase F leads to a decrease in its apparent molecular mass by approximately 12 kDa, suggesting that the extent of glycosylation of this polypeptide is approximately 25%. As shown in the following paper, the intact protein constitutes a Ca2+ channel that is activated upon IgE-Fc epsilon receptor aggregation.

Affinity Labels↗
PubMed1987

The role of the murine L3T4 molecule in T cell activation: differential effects of anti-L3T4 on activation by monoclonal anti-receptor antibodies.

MHC restricted T cells can be divided into two subsets based on the mutually exclusive expression of the cell surface differentiation antigens L3T4 and Lyt-2 in the mouse. Expression of the L3T4 marker is correlated most strictly with recognition of foreign antigen in association with self class II MHC molecules, or Ia molecules. Less stringently correlated with L3T4 expression is the recognition of unmodified self or non-self Ia molecules. Finally, expression of L3T4 is also correlated with certain functional properties, although this correlation is even less stringent. The major correlation for function is between L3T4 and the ability to activate B cells. These correlations have led to the hypothesis that L3T4 recognizes Ia molecules, and plays a role in increasing the affinity of T cell:Ia bearing cell interactions. This hypothesis is bolstered by the finding that anti-L3T4 antibody blocks such interactions. Recently, we and others proposed a second effect of cross-linking L3T4 molecules, namely negative signalling. We further proposed that the natural ligand for L3T4 is Ia molecules, and that Ia-driven cross-linking of L3T4 molecules on the T cell in the absence of receptor aggregation would lead to off signalling to the T cell and separation of cell conjugates. To better understand the role of the L3T4 molecule in T cell activation, we have examined the effect of several anti-L3T4 antibodies on stimulation of a cloned line of helper T cells by a panel of monoclonal antibodies directed at what appear to be different epitopes on the T cell receptor. Unlike previous analyses of stimulation of helper T cells with anti-T cell receptor antibodies, we observe differential effects of anti-L3T4 on T cell activation by anti-receptor antibodies, the effect of anti-L3T4 depending on the characteristics of the anti-receptor antibody. This result suggests that L3T4 is intimately associated with the T cell receptor, and may thus play a critical role in T cell specificity as part of the antigen:Ia recognition complex. This proposed role is in keeping with the very strong correlation between L3T4 expression and recognition of self class II MHC molecules. While these studies do not provide definitive evidence for a physical association between L3T4 and the T cell receptor, they do place certain constraints on current models and suggest new possibilities for understanding T cell recognition and development.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

95 kd sperm proteins bind ZP3 and serve as tyrosine kinase substrates in response to zona binding.

In the mouse, the zona pellucida (ZP) glycoprotein ZP3 both binds intact sperm and induces acrosomal exocytosis. The subsequent signaling pathway(s) is still uncertain, but Gi-like proteins have been implicated. By analogy with other signal transduction mechanisms, we examined anti-phosphotyrosine antibody reactivity in mouse sperm. Antibodies reacted with three proteins of 52, 75, and 95 kd. Indirect immunofluorescence localized reactivity to the acrosomal region of the sperm head. The 52 kd and 75 kd phosphoproteins are detected only in capacitated sperm, whereas the 95 kd protein is detected in both fresh and capacitated sperm. For the 95 kd protein, the level of immunoreactivity is not related to sperm motility but is enhanced by both capacitation and sperm interaction with solubilized ZP proteins. In addition, binding of radiolabeled whole ZP or purified ZP3 to blots of separated sperm proteins identified two ZP binding proteins of 95 kd and 42 kd. 95 kd sperm proteins that bind to ZP3 also react with anti-phosphotyrosine antibodies (in a ZP concentration-dependent manner), supporting the idea that the same 95 kd sperm protein serves as a ZP3 receptor and as a tyrosine kinase substrate. These findings and our evidence on acrosome reaction triggering via sperm receptor aggregation suggest that a 95 kd protein in the sperm plasma membrane is aggregated by ZP3, which stimulates tyrosine kinase activity leading to acrosomal exocytosis.

Acrosome↗
PubMed1996

Transmitter concentration profiles in the synaptic cleft: an analytical model of release and diffusion.

A three-dimensional model for release and diffusion of glutamate in the synaptic cleft was developed and solved analytically. The model consists of a source function describing transmitter release from the vesicle and a diffusion function describing the spread of transmitter in the cleft. Concentration profiles of transmitter at the postsynaptic side were calculated for different transmitter concentrations in a vesicle, release scenarios, and diffusion coefficients. From the concentration profiles the receptor occupancy could be determined using alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor kinetics. It turned out that saturation of receptors and sufficiently fast currents could only be obtained if the diffusion coefficient was one order of magnitude lower than generally assumed, and if the postsynaptic receptors formed clusters with a diameter of roughly 100 nm directly opposite the release sites. Under these circumstances the gradient of the transmitter concentration at the postsynaptic membrane outside the receptor clusters was steep, with minimal cross-talk among neighboring receptor clusters. These findings suggest that for each release site a corresponding receptor aggregate exists, subdividing an individual synapse into independent functional subunits without the need for specific lateral diffusion barriers.

Animals↗
PubMed1999

Crystal structure of the HLA-Cw3 allotype-specific killer cell inhibitory receptor KIR2DL2.

Killer cell inhibitory receptors (KIR) protect class I HLAs expressing target cells from natural killer (NK) cell-mediated lysis. To understand the molecular basis of this receptor-ligand recognition, we have crystallized the extracellular ligand-binding domains of KIR2DL2, a member of the Ig superfamily receptors that recognize HLA-Cw1, 3, 7, and 8 allotypes. The structure was determined in two different crystal forms, an orthorhombic P212121 and a trigonal P3221 space group, to resolutions of 3.0 and 2.9 A, respectively. The overall fold of this structure, like KIR2DL1, exhibits K-type Ig topology with cis-proline residues in both domains that define beta-strand switching, which sets KIR apart from the C2-type hematopoietic growth hormone receptor fold. The hinge angle of KIR2DL2 is approximately 80 degrees, 14 degrees larger than that observed in KIR2DL1 despite the existence of conserved hydrophobic residues near the hinge region. There is also a 5 degrees difference in the observed hinge angles in two crystal forms of 2DL2, suggesting that the interdomain hinge angle is not fixed. The putative ligand-binding site is formed by residues from several variable loops with charge distribution apparently complementary to that of HLA-C. The packing of the receptors in the orthorhombic crystal form offers an intriguing model for receptor aggregation on the cell surface.

Amino Acid Sequence↗
PubMed1995

Effects of subunit mutation on the rotational dynamics of Fc epsilon RI, the high affinity receptor for IgE, in transfected cells.

Erythrosin-labeled immunoglobulin E (IgE) and time-resolved phosphorescence anisotropy were used to monitor the rotational dynamics of transfected wild-type (alpha beta gamma 2) and four mutant Fc epsilon RI receptors in the monomeric and dimeric state on P815 cells. Erythrosin-IgE bound to Fc epsilon RI on cells transfected with either beta or gamma subunits with truncated COOH-terminal cytoplasmic segments exhibit faster rotational motion than when bound to Fc epsilon RI on cells transfected with wild-type subunits. Deletion of the NH2-terminal cytoplasmic segment of the beta subunit or the COOH-terminal cytoplasmic segment of the alpha subunit does not cause any significant change in the anisotropy decay. Dimers of IgE-receptor complexes formed with anti-IgE monoclonal antibody B1E3 exhibit substantially slower anisotropy decays for all the receptor constructs used, including a receptor construct that only contains the ectodomain of the alpha subunit anchored to Chinese hamster ovary (CHO) cell membranes through a lipid tail. This loss of rotational motion of dimeric IgE-Fc epsilon RI complexes may be due to nonspecific entanglement or to specific interactions involving IgE or the extracellular portion of alpha. The results suggest that the beta and gamma subunits of the tetrameric alpha beta gamma 2 receptor participate in interactions with other membrane components even in the absence of receptor aggregation. The loss of such interactions may be related to the functional impairments previously determined for these mutants.

Animals↗
PubMed1998

Effects of reteplase and alteplase on platelet aggregation and major receptor expression during the first 24 hours of acute myocardial infarction treatment. GUSTO-III Investigators. Global Use of Strategies to Open Occluded Coronary Arteries.

OBJECTIVES: We sought to compare platelet characteristics after reteplase and alteplase therapy in the setting of the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO)-III trial. BACKGROUND: Platelet function may be impaired during thrombolysis in patients with an acute myocardial infarction. The effects of reteplase and alteplase on platelet aggregation and major surface antigen expression during the first 24 h of infarction therapy are unknown. METHODS: Platelet aggregation and receptor expression by flow cytometry were determined in 23 patients before thrombolysis and thereafter at 3, 6, 12 and 24 h. RESULTS: Aggregation was higher after reteplase at 24 h when induced by 5 micromol/liter adenosine diphosphate (ADP) (p = 0.007), 10 micromol/liter ADP (p = 0.02), collagen (p = 0.003) and thrombin (p = 0.009) than after alteplase. Reteplase therapy exhibited greater glycoprotein (GP) IIb/IIIa (p = 0.04), very late antigen-2 (p = 0.04) and platelet/endothelial cell adhesion molecule-I (p = 0.002) expression at 24 h. Trends toward decreased receptor expression early (3 to 6 h), followed by a progressive increase at 12 h and especially at 24 h occurred after both agents. CONCLUSIONS: In this prospective clinical ex vivo platelet study, similar patterns of platelet aggregation and surface receptor expression occurred during the first 24 h of coronary thrombolysis with reteplase and alteplase. However, after reteplase, indicators of platelet activity were higher at 24 h after thrombolysis than after alteplase. These data suggest that GP IIb/IIIa inhibitors or other antiplatelet strategies may be particularly advantageous when used 12 to 24 h after thrombolysis, especially after reteplase therapy. It is at this time point during the first day of coronary thrombolysis that GP IIb/IIIa is markedly expressed and platelets are most active.

Adult↗
PubMed1983

Measurement of the binding activity of defined IgG aggregates to macrophage Fc receptors.

Small soluble IgG aggregates of defined size were prepared from pooled human IgG by gel filtration chromatography, and examined by analytical ultracentrifugation. Three such fractions, dimer-rich, trimer-rich and 25S aggregate were used to inhibit IgG monomer binding in a study of the influence of aggregation in the binding of human IgG1 to mouse macrophage Fc receptors. Of the polymers tested, IgG in the trimeric form was found to bind with the greatest avidity, being 158 times more active than monomeric IgG, whereas IgG as a larger 25S aggregate had an increased binding activity of 80 times; the avidity of IgG as dimer was increased by a factor of 2 over monomeric IgG. The possible mechanisms involved in achieving enhanced binding are discussed.

Animals↗
PubMed2001

Sphingolipids in mammalian cell signalling.

Sphingolipids and their metabolites, ceramide, sphingosine and sphingosine-1-phosphate, are involved in a variety of cellular processes including differentiation, cellular senescence, apoptosis and proliferation. Ceramide is the main second messenger, and is produced by sphingomyelinase-induced hydrolysis of sphingomyelin and by de novo synthesis. Many stimuli, e. g. growth factors, cytokines, G protein-coupled receptor agonists and stress (UV irradiation) increase cellular ceramide levels. Sphingomyelin in the plasma membrane is located primarily in the outer (extracellular) leaflet of the bilayer, whilst sphingomyelinases are found at the inner (cytosolic) face and within lysosomes/endosomes. Such cellular compartmentalisation restricts the site of ceramide production and subsequent interaction with target proteins. Glycosphingolipids and sphingomyelin together with cholesterol are major components of specialised membrane microdomains known as lipid rafts, which are involved in receptor aggregation and immune responses. Many signalling molecules, for example Src family tyrosine kinases and glycosylinositolphosphate-anchored proteins, are associated with rafts, and disruption of these domains affects cellular responses such as apoptosis. Sphingosine and sphingosine-1-phosphate derived from ceramide are also signalling molecules. In particular, sphingosine-1-phosphate is involved in proliferation, differentiation and apoptosis. Sphingosine-1-phosphate can act both extracellularly through endothelial-differentiating gene (EDG) family G protein-coupled receptors and intracellularly through direct interactions with target proteins. The importance of sphingolipid signalling in cardiovascular development has been reinforced by recent reports implicating EDG receptors in the regulation of embryonic cardiac and vascular morphogenesis.

Animals↗
PubMed1994

Fibronectin receptor integrins are involved in mast cell activation.

Mast cells express fibronectin-receptor integrins on the cell surface, which are involved in cellular activation. In this study rat and mouse mast cells adhered to fibronectin through very late antigen 4, 5 (beta 1 integrin) and vitronectin receptor (beta 3 integrin), and engagement of these receptors promoted cellular degranulation induced by cross-linking of the high-affinity IgE receptor. Blocking of these adhesion molecules by monoclonal antibodies remarkably reduced passive cutaneous anaphylaxis reaction in vivo. On fibronectin, cytokine release from mast cells on IgE receptor aggregation was also enhanced, but not the expression of cytokine genes, with the exception of interleukin-3. Interleukin-3 gene expression was constitutively observed in mouse-cultured mast cells and significantly increased on fibronectin with a prolonged survival of the cells, suggesting that the autocrine or paracrine system of interleukin-3 secretion contributes to the prolonged survival of mast cells on fibronectin. Our findings presented here clearly indicate that the engagement of fibronectin-receptor integrins on mast cells increases the sensitivity of the cells for cellular activation. Taking into consideration the fact that mast cells in the microenvironment are actually surrounded by other cells and extracellular matrix proteins, we identified significant roles of adhesion molecules on mast cells in the allergic state, and we hope to develop new strategies to manipulate these molecules for medical intervention in allergy.

Animals↗
PubMed2001

The structure of a human type III Fcgamma receptor in complex with Fc.

Fcgamma receptors mediate antibody-dependent inflammatory responses and cytotoxicity as well as certain autoimmune dysfunctions. Here we report the crystal structure of a human Fc receptor (FcgammaRIIIB) in complex with an Fc fragment of human IgG1 determined from orthorhombic and hexagonal crystal forms at 3.0- and 3.5-A resolution, respectively. The refined structures from the two crystal forms are nearly identical with no significant discrepancies between the coordinates. Regions of the C-terminal domain of FcgammaRIII, including the BC, C'E, FG loops, and the C' beta-strand, bind asymmetrically to the lower hinge region, residues Leu(234)-Pro(238), of both Fc chains creating a 1:1 receptor-ligand stoichiometry. Minor conformational changes are observed in both the receptor and Fc upon complex formation. Hydrophobic residues, hydrogen bonds, and salt bridges are distributed throughout the receptor.Fc interface. Sequence comparisons of the receptor-ligand interface residues suggest a conserved binding mode common to all members of immunoglobulin-like Fc receptors. Structural comparison between FcgammaRIII.Fc and FcepsilonRI.Fc complexes highlights the differences in ligand recognition between the high and low affinity receptors. Although not in direct contact with the receptor, the carbohydrate attached to the conserved glycosylation residue Asn(297) on Fc may stabilize the conformation of the receptor-binding epitope on Fc. An antibody-FcgammaRIII model suggests two possible ligand-induced receptor aggregations.

Amino Acid Sequence↗
PubMed1985

Trypsin cleavage of chick 1,25-dihydroxyvitamin D3 receptors. Generation of discrete polypeptides which retain hormone but are unreactive to DNA and monoclonal antibody.

Intestinal cytosol receptors for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) were subjected to limited trypsin digestion, and the properties of the resulting discrete polypeptide fragments were identified and contrasted with the native 1,25(OH)2D3 receptor. Physical characterization was achieved through sedimentation analysis, gel filtration chromatography, and DEAE anion exchange high performance liquid chromatography. Intactness of functional ligand-binding domains was evaluated by assessing macromolecular retention of 1,25(OH)2D3 as well as by determining reactivity to DNA and monoclonal antibody. While two differentially trypsin-sensitive effects on the 1,25(OH)2D3 receptor were noted, both produced a major polypeptide fragment which retained 1,25(OH)2D3. Action within region I (1 microgram of trypsin/A280-A310) had no effect on net charge but significantly decreased the Stokes radius of the 1,25(OH)2D3 receptor from 3.6 nm (60,000 daltons) to 3.2 nm, concomitant with a significant reduction in receptor aggregational capacity. This large hormone-bound fragment did not elicit detectable DNA-binding activity, and only a portion displayed reactivity to monoclonal antibody. Activity within region II (25 micrograms of trypsin/A280-A310) resulted in a less charged, more globular macromolecule with a Stokes radius of 2.9 nm which was completely unreactive to monoclonal antibody. Immunoblot methodology confirmed the protease-dependent loss of immunologic reactivity of the 60,000-dalton 1,25(OH)2D3 receptor and correspondingly identified receptor fragments of 50,000 and 20,000 daltons displaying positive immunologic reactivity. These studies provide the first evidence for the distinct nature of the molecular domains for 1,25(OH)2D3 and DNA on 1,25(OH)2D3 receptors while confirming the close spatial relationship between interactive sites for DNA and monoclonal antibody.

Animals↗
PubMed2000

Crystal structure of the extracellular domain of a human Fc gamma RIII.

Fc receptors play a major role in immune defenses against pathogens and in inflammatory processes. The crystal structure of a human immunoglobulin receptor, FcgammaRIIIb, has been determined to 1.8 A resolution. The overall fold consists of two immunoglobulin-like domains with an acute interdomain hinge angle of approximately 50 degrees. Trp-113, wedged between the N-terminal D1 and the C-terminal D2 domains, appears to further restrict the hinge angle. The putative Fc binding region of the receptor carries a net positive charge complementary to the negative-charged receptor binding regions on Fc. A 1:1 binding stoichiometry between the receptor and Fc was measured by both the equilibrium and nonequilibrium size-exclusion chromatography. Two separate parallel dimers are observed in the crystal lattice, offering intriguing models for receptor aggregation.

Amino Acid Sequence↗