A Positive Cooperativity Binding Model between Ly49 Natural Killer Cell Receptors and the Viral Immunoevasin m157

Romasanta, Pablo Nicolás; Curto, Lucrecia María; Urtasun, Nicolás; Sarratea, María Belén; Chiappini, Santiago Andrés; Miranda, Magdalena; Delfino, José M.; Mariuzza, Roy A.; Fernández, María Elena Márquez; Malchiodi, Emilio L.

doi:10.1074/jbc.m113.532929

Cited by 7 publications

(2 citation statements)

References 39 publications

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“…In agreement with the model, biochemical analyses confirmed that trans binding of MHC-I by Ly49 dimers occurs in a bivalent fashion, whereas cis binding is monovalent ( 106 ). Moreover, Ly49 receptors appear able to switch between backfolded and extended conformations ( 108 , 123 ).…”

Section: Trans and Cis Interactions Of Lymentioning

confidence: 99%

“…In the backfolded conformation, by contrast, the Ly49 α3s stalk segment would not be accessible to m157, due to its intimate association with the NKD (Figure 8 A). For both the Ly49H–m157 and Ly49I–m157 interactions, kinetic and thermodynamic measurements showed that binding involves a conformational selection mechanism where only the extended conformation of Ly49 is able to bind a first m157 ligand, followed by binding of a second m157 ( 123 ). The interaction is characterized by strong positive cooperativity, such that the second m157 binds the Ly49 homodimer 1,000-fold more tightly than the first.…”

Section: Ly49 Recognition Of a Viral Immunoevasinmentioning

confidence: 99%

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Structural Basis for Recognition of Cellular and Viral Ligands by NK Cell Receptors

Mariuzza

2014

Front. Immunol.

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Natural killer (NK) cells are key components of innate immune responses to tumors and viral infections. NK cell function is regulated by NK cell receptors that recognize both cellular and viral ligands, including major histocompatibility complex (MHC), MHC-like, and non-MHC molecules. These receptors include Ly49s, killer immunoglobulin-like receptors, leukocyte immunoglobulin-like receptors, and NKG2A/CD94, which bind MHC class I (MHC-I) molecules, and NKG2D, which binds MHC-I paralogs such as the stress-induced proteins MICA and ULBP. In addition, certain viruses have evolved MHC-like immunoevasins, such as UL18 and m157 from cytomegalovirus, that act as decoy ligands for NK receptors. A growing number of NK receptor–ligand interaction pairs involving non-MHC molecules have also been identified, including NKp30–B7-H6, killer cell lectin-like receptor G1–cadherin, and NKp80–AICL. Here, we describe crystal structures determined to date of NK cell receptors bound to MHC, MHC-related, and non-MHC ligands. Collectively, these structures reveal the diverse solutions that NK receptors have developed to recognize these molecules, thereby enabling the regulation of NK cytolytic activity by both host and viral ligands.

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Section: Trans and Cis Interactions Of Lymentioning

confidence: 99%

Section: Ly49 Recognition Of a Viral Immunoevasinmentioning

confidence: 99%

Structural Basis for Recognition of Cellular and Viral Ligands by NK Cell Receptors

Mariuzza

2014

Front. Immunol.

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MCMV avoidance of recognition and control by NK cells

et al. 2014

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Natural killer (NK) cells play an important role in virus control during infection. Many viruses have developed mechanisms for subversion of NK cell responses. Murine cytomegalovirus (MCMV) is exceptionally successful in avoiding NK cell control. Here, we summarize the major MCMV evasion mechanisms targeting NK cell functions and their role in viral pathogenesis. The mechanisms by which NK cells regulate CD8(+) T cell response, particularly with respect to the role of NK cell receptors recognizing viral antigens, are discussed. In addition, we discuss the role of NK cell receptors in generation and maintenance of memory NK cells. Final part of this review illustrates how the NK cell response and its viral regulation can be exploited in designing recombinant viral vectors able to induce robust and protective CD8(+) T cell response.

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Natural Killer Cell Receptors

Rangarajan

Mariuzza

2018

Structural Biology in Immunology

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A Positive Cooperativity Binding Model between Ly49 Natural Killer Cell Receptors and the Viral Immunoevasin m157

Cited by 7 publications

References 39 publications

Structural Basis for Recognition of Cellular and Viral Ligands by NK Cell Receptors

Structural Basis for Recognition of Cellular and Viral Ligands by NK Cell Receptors

MCMV avoidance of recognition and control by NK cells

Natural Killer Cell Receptors

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