NMR Structure of the Natural Killer Cell Receptor 2B4 (CD244):  Implications for Ligand Recognition,

Ames, James B.; Vyas, Vinay V.; Lusin, Jacqueline D.; Mariuzza, Roy A.

doi:10.1021/bi0580097

Cited by 4 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A soluble version of 2B4, consisting of the ligand-binding IgV domain alone, was expressed in bacterial inclusion bodies and folded in vitro as described previously (Ames et al, 2005). However, initial attempts to produce the IgV portion of CD48 by this approach were unsuccessful, possibly because of the instability of the isolated domain.…”

Section: Structure Determinationmentioning

confidence: 99%

“…The ligand-binding domain of 2B4 (residues 1-112) from C57BL/6 mice was expressed by in vitro folding from Escherichia coli inclusion bodies as described (Ames et al, 2005). Mutants of 2B4 (K35A, R43A, E91A, T93A, and T95A) were produced and purified similarly to the wild-type protein.…”

Section: Protein Expression and Purificationmentioning

confidence: 99%

“…Despite the importance of 2B4-CD48 interactions for the regulation of NK cell activity, structural studies have been confined to the individual proteins: a solution nuclear magnetic resonance (NMR) structure of mouse 2B4 (Ames et al, 2005) and an X-ray crystal structure of rat CD48 (Evans et al, 2006). To understand 2B4-CD48 recognition, we determined the crystal structures of mouse 2B4 and CD48 in both bound and free forms and identified key interactions through the mutational analysis of 2B4.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Structure of Natural Killer Receptor 2B4 Bound to CD48 Reveals Basis for Heterophilic Recognition in Signaling Lymphocyte Activation Molecule Family

et al. 2007

View full text Add to dashboard Cite

Natural killer (NK) cells eliminate virally infected and tumor cells. Among the receptors regulating NK cell function is 2B4 (CD244), a member of the signaling lymphocyte-activation molecule (SLAM) family that binds CD48. 2B4 is the only heterophilic receptor of the SLAM family, whose other members, e.g., NK-T-B-antigen (NTB-A), are self-ligands. We determined the structure of the complex between the N-terminal domains of mouse 2B4 and CD48, as well as the structures of unbound 2B4 and CD48. The complex displayed an association mode related to, yet distinct from, that of the NTB-A dimer. Binding was accompanied by the rigidification of flexible 2B4 regions containing most of the polymorphic residues across different species and receptor isoforms. We propose a model for 2B4-CD48 interactions that permits the intermixing of SLAM receptors with major histocompatibility complex-specific receptors in the NK cell immune synapse. This analysis revealed the basis for heterophilic recognition within the SLAM family.

show abstract

Section: Structure Determinationmentioning

confidence: 99%

Section: Protein Expression and Purificationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Structure of Natural Killer Receptor 2B4 Bound to CD48 Reveals Basis for Heterophilic Recognition in Signaling Lymphocyte Activation Molecule Family

et al. 2007

View full text Add to dashboard Cite

show abstract

“…NTB-A and CD2 (Wang et al, 1999) exhibit a root mean square deviation (RMSD) of w1.5 Å based on 86 equivalent Ca atoms, confirming their structural similarity. Similarly, NTB-A and 2B4 exhibit an RMSD of w2.2 Å (86 Ca) (Ames et al, 2005), and NTB-A and CD58 exhibit an RMSD of w1.7 Å (87 Ca) (Wang et al, 1999). Whereas the overall disposition of the b strands of these IgV domains is highly similar, the loops exhibit considerable diversity in both length and orientation.…”

Section: The N-terminal Igv Domainmentioning

confidence: 99%

“…Specifically, NTB-A, CRACC, CD84, SLAM, and Ly-9 are homophilic receptors because they are selfligands, whereas CD48 and CD2 participate in heterophilic interactions with 2B4 and CD58, respectively (Engel et al, 2003). The X-ray structures of CD2 (Bodian et al, 1994;Jones et al, 1992), CD58 (Ikemizu et al, 1999), and the CD2-CD58 heterophilic complex (Wang et al, 1999), as well as the NMR structure of 2B4 (Ames et al, 2005) have been reported. Despite the importance of homophilic interactions within the SLAM family, there are no data addressing several important issues, including the structural similarities and differences between homophilic and heterophilic interactions, a mechanistic explanation for the wide range of affinities associated with homophilic interactions, and the signal-transduction mechanisms utilized by the SLAM-family receptors.…”

Section: Introductionmentioning

confidence: 99%

NTB-A Receptor Crystal Structure: Insights into Homophilic Interactions in the Signaling Lymphocytic Activation Molecule Receptor Family

et al. 2006

View full text Add to dashboard Cite

The signaling lymphocytic activation molecule (SLAM) family includes homophilic and heterophilic receptors that regulate both innate and adaptive immunity. The ectodomains of most SLAM family members are composed of an N-terminal IgV domain and a C-terminal IgC2 domain. NK-T-B-antigen (NTB-A) is a homophilic receptor that stimulates cytotoxicity in natural killer (NK) cells, regulates bactericidal activities in neutrophils, and potentiates T helper 2 (Th2) responses. The 3.0 A crystal structure of the complete NTB-A ectodomain revealed a rod-like monomer that self-associates to form a highly kinked dimer spanning an end-to-end distance of approximately 100 A. The NTB-A homophilic and CD2-CD58 heterophilic dimers show overall structural similarities but differ in detailed organization and physicochemical properties of their respective interfaces. The NTB-A structure suggests a mechanism responsible for binding specificity within the SLAM family and imposes physical constraints relevant to the colocalization of SLAM-family proteins with other signaling molecules in the immunological synapse.

show abstract

NK cell recognition of hematopoietic cells by SLAM-SAP families

Chen¹,

Dong²

2019

Cell Mol Immunol

View full text Add to dashboard Cite

The signaling lymphocyte activation molecule (SLAM) family of receptors (SFRs) are ubiquitously expressed on immune cells, and they regulate multiple immune events by recruiting SH2 (Src homology 2) domain-containing SAP family adapters, including SAP and its homologs, Ewing's sarcoma-associated transcript 2 (EAT-2) and EAT-2 related transducer (ERT). In human patients with X-linked lymphoproliferative (XLP) disease, which is caused by SAP mutations, SFRs alternatively bind other inhibitory SH2 domaincontaining molecules to suppress immune cell activation and development. NK cells express multiple SFRs and all SAP family adapters. In recent decades, SFRs have been found to be critical for enhancing NK cell activation in response to abnormal hematopoietic cells in SAP-family-intact NK cells; however, SFRs might suppress NK cell activation in SAP-family-deficient mice or patients with XLP1. In this paper, we review how these two distinct SFR signaling pathways orchestrate NK cell activation and inhibition and highlight the importance of SFR regulation of NK cell biology and their physiological status and pathological relevance in patients with XLP1.

show abstract

NMR Structure of the Natural Killer Cell Receptor 2B4 (CD244): Implications for Ligand Recognition,

Cited by 4 publications

References 0 publications

Structure of Natural Killer Receptor 2B4 Bound to CD48 Reveals Basis for Heterophilic Recognition in Signaling Lymphocyte Activation Molecule Family

Structure of Natural Killer Receptor 2B4 Bound to CD48 Reveals Basis for Heterophilic Recognition in Signaling Lymphocyte Activation Molecule Family

NTB-A Receptor Crystal Structure: Insights into Homophilic Interactions in the Signaling Lymphocytic Activation Molecule Receptor Family

NK cell recognition of hematopoietic cells by SLAM-SAP families

Contact Info

Product

Resources

About