FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2913939588> ?p ?o ?g. }

• W2913939588 endingPage "210" @default.
• W2913939588 startingPage "209" @default.
• W2913939588 abstract "The cytolytic activity of NK cells is regulated by activating and inhibitory receptors, including ones that recognize cell–cell adhesion molecules. In this issue of Structure, Deuss et al., 2019Deuss F.A. Watson G.M. Fu Z. Rossjohn J. Berry R. Structural basis for CD96 immune receptor recognition of nectin-like protein-5 (CD155).Structure. 2019; 27 (this issue): 219-228Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar report the structure of nectin-like protein-5 bound to the NK inhibitory receptor CD96, a promising new target for cancer immunotherapy. The cytolytic activity of NK cells is regulated by activating and inhibitory receptors, including ones that recognize cell–cell adhesion molecules. In this issue of Structure, Deuss et al., 2019Deuss F.A. Watson G.M. Fu Z. Rossjohn J. Berry R. Structural basis for CD96 immune receptor recognition of nectin-like protein-5 (CD155).Structure. 2019; 27 (this issue): 219-228Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar report the structure of nectin-like protein-5 bound to the NK inhibitory receptor CD96, a promising new target for cancer immunotherapy. Natural killer (NK) cells are essential components of the innate immune system with the ability to recognize and rapidly eliminate virally infected and malignantly transformed cells. The cytolytic activity of NK cells is controlled by a dynamic interplay between a multitude of positive signaling activating receptors (resulting in target cell lysis) and negative signaling inhibitory receptors (preventing lysis). (Long et al., 2013Long E.O. Kim H.S. Liu D. Peterson M.E. Rajagopalan S. Controlling natural killer cell responses: integration of signals for activation and inhibition.Annu. Rev. Immunol. 2013; 31: 227-258Crossref PubMed Scopus (798) Google Scholar). Integration of signals from these opposing receptors determines the ultimate outcome of NK cell–target cell encounters. NK receptors belong to two distinct structural families: the C-type lectin superfamily and the immunoglobulin (Ig) superfamily (Li and Mariuzza, 2014Li Y. Mariuzza R.A. Structural basis for recognition of cellular and viral ligands by NK cell receptors.Front. Immunol. 2014; 5: 123Crossref PubMed Scopus (49) Google Scholar). Both superfamilies include activating (e.g., DNAM-1, NKp30, 2B4, NKG2D) and inhibitory (e.g., KIRs, Ly49s, NKG2A/CD94, CD96) receptors that recognize remarkably diverse cellular or viral ligands, including major histocompatibility complex (MHC), MHC-like, and non-MHC molecules. The dominant signal received by an NK cell is inhibitory, provided mainly by the interaction of KIRs (in humans) and Ly49s (in rodents) with normal levels of MHC class I molecules on the surface of target cells (Long et al., 2013Long E.O. Kim H.S. Liu D. Peterson M.E. Rajagopalan S. Controlling natural killer cell responses: integration of signals for activation and inhibition.Annu. Rev. Immunol. 2013; 31: 227-258Crossref PubMed Scopus (798) Google Scholar). If infectious or tumorigenic processes reduce MHC class I expression, this inhibitory signal is attenuated, and the NK cell undergoes activation. As a result, cells with reduced MHC class I expression become subject to lysis by NK cells. In addition to MHC class I, a growing number of non-MHC molecules have been identified that bind to other inhibitory receptors, thereby helping prevent tissue damage by NK cells. Among these surprising non-MHC ligands are nectins, nectin-like proteins, and cadherins (Long et al., 2013Long E.O. Kim H.S. Liu D. Peterson M.E. Rajagopalan S. Controlling natural killer cell responses: integration of signals for activation and inhibition.Annu. Rev. Immunol. 2013; 31: 227-258Crossref PubMed Scopus (798) Google Scholar). These molecules are type I transmembrane glycoproteins comprising multiple Ig-like domains that mediate cell–cell adhesion and various other cellular functions, such as movement and polarization, through homotypic or heterotypic interactions (Rikitake et al., 2012Rikitake Y. Mandai K. Takai Y. The role of nectins in different types of cell-cell adhesion.J. Cell Sci. 2012; 125: 3713-3722Crossref PubMed Scopus (104) Google Scholar, Harrison et al., 2011Harrison O.J. Jin X. Hong S. Bahna F. Ahlsen G. Brasch J. Wu Y. Vendome J. Felsovalyi K. Hampton C.M. et al.The extracellular architecture of adherens junctions revealed by crystal structures of type I cadherins.Structure. 2011; 19: 244-256Abstract Full Text Full Text PDF PubMed Scopus (276) Google Scholar). In this issue of Structure, Deuss et al., 2019Deuss F.A. Watson G.M. Fu Z. Rossjohn J. Berry R. Structural basis for CD96 immune receptor recognition of nectin-like protein-5 (CD155).Structure. 2019; 27 (this issue): 219-228Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar report the crystal structure of the NK inhibitory receptor CD96 in complex with nectin-like protein-5 (necl-5; CD155) (Figure 1A). In addition to deepening our appreciation of the multiplicity of solutions NK receptors have evolved to recognize non-MHC ligands (Li and Mariuzza, 2014Li Y. Mariuzza R.A. Structural basis for recognition of cellular and viral ligands by NK cell receptors.Front. Immunol. 2014; 5: 123Crossref PubMed Scopus (49) Google Scholar), the CD96–necl-5 structure is of special interest because CD96 has emerged as potential target for human cancer immunotherapy (Georgiev et al., 2018Georgiev H. Ravens I. Papadogianni G. Bernhardt G. Coming of age: CD96 emerges as modulator of immune responses.Front. Immunol. 2018; 9: 1072Crossref PubMed Scopus (56) Google Scholar). Necl-5 binds to nectin-3 to assist in the establishment of adherens junctions between tissue cells (Rikitake et al., 2012Rikitake Y. Mandai K. Takai Y. The role of nectins in different types of cell-cell adhesion.J. Cell Sci. 2012; 125: 3713-3722Crossref PubMed Scopus (104) Google Scholar). Necl-5 is often highly upregulated on tumor cells and increased expression of necl-5 correlates with poor prognosis and enhanced resistance to chemotherapy, most likely through inhibition of killing by NK cells expressing CD96. Consistent with this idea, blocking the CD96–necl-5 interaction in vivo with anti-CD96 monoclonal antibodies inhibited experimental metastases in several mouse tumor models (Georgiev et al., 2018Georgiev H. Ravens I. Papadogianni G. Bernhardt G. Coming of age: CD96 emerges as modulator of immune responses.Front. Immunol. 2018; 9: 1072Crossref PubMed Scopus (56) Google Scholar). In this regard, antibodies that enhance T cell anti-tumor immune responses by blocking the interaction of the T cell inhibitory receptors CTLA-4 and PD-1 with inhibitory ligands on tumor cells (so-called immune checkpoint inhibitors) have proven very successful therapeutics. The extracellular portions of CD96 and necl-5 each possess three contiguous Ig-like domains. However, both solution binding measurements and the crystal structure indicate that the CD96–necl-5 interaction involves only the first Ig-like domain (D1) of each partner (Deuss et al., 2019Deuss F.A. Watson G.M. Fu Z. Rossjohn J. Berry R. Structural basis for CD96 immune receptor recognition of nectin-like protein-5 (CD155).Structure. 2019; 27 (this issue): 219-228Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar) (Figure 1A). The overall docking topology is similar to that observed previously for TIGIT, an NK inhibitory receptor closely related to CD96, bound to nectin-2 (Deuss et al., 2017Deuss F.A. Gully B.S. Rossjohn J. Berry R. Recognition of nectin-2 by the natural killer cell receptor T cell immunoglobulin and ITIM domain (TIGIT).J. Biol. Chem. 2017; 292: 11413-11422Crossref PubMed Scopus (51) Google Scholar). CD96 and TIGIT recognize their respective ligands using a conserved “lock-and-key” binding motif also found in nectin/necl homo- and heterodimers. However, CD96 differs markedly from TIGIT in terms of specificity: whereas TIGIT binds nectin-2, nectin-3 and necl-5, CD96 only recognizes necl-5. The more restricted specificity of CD96 appears due to a small shift in the position of CD96 D1 away from the CC″ loop of necl-5, leading to loss of contacts with the FG loop of the receptor that stabilize the TIGIT–nectin-2 complex. The CD96–necl-5 complex may be compared with the first reported complex between an NK receptor and a cell–cell adhesion protein, involving killer cell lectin-like receptor G1 (KLRG1) and E-cadherin (Li et al., 2009Li Y. Hofmann M. Wang Q. Teng L. Chlewicki L.K. Pircher H. Mariuzza R.A. Structure of natural killer cell receptor KLRG1 bound to E-cadherin reveals basis for MHC-independent missing self recognition.Immunity. 2009; 31: 35-46Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar) (Figure 1B). Like CD96, KLRG1 is an inhibitory receptor expressed on most NK cells. However, whereas CD96 is a type I transmembrane protein comprising three extracellular Ig-like domains, KLRG1 is a type II transmembrane protein composed of a single extracellular C-type lectin-like domain connected by a short stalk to transmembrane and cytoplasmic segments. Cadherins mediate Ca2+-dependent cell–cell adhesion via homotypic interactions (Harrison et al., 2011Harrison O.J. Jin X. Hong S. Bahna F. Ahlsen G. Brasch J. Wu Y. Vendome J. Felsovalyi K. Hampton C.M. et al.The extracellular architecture of adherens junctions revealed by crystal structures of type I cadherins.Structure. 2011; 19: 244-256Abstract Full Text Full Text PDF PubMed Scopus (276) Google Scholar), while nectins and nectin-like proteins mediate Ca2+-independent adhesion through both homo- and heterotypic interactions (Rikitake et al., 2012Rikitake Y. Mandai K. Takai Y. The role of nectins in different types of cell-cell adhesion.J. Cell Sci. 2012; 125: 3713-3722Crossref PubMed Scopus (104) Google Scholar). The biological ligand of KLGR1 is E-cadherin (Long et al., 2013Long E.O. Kim H.S. Liu D. Peterson M.E. Rajagopalan S. Controlling natural killer cell responses: integration of signals for activation and inhibition.Annu. Rev. Immunol. 2013; 31: 227-258Crossref PubMed Scopus (798) Google Scholar), whose extracellular region consists of five contiguous Ig-like domains. E-cadherin is located at the basolateral membrane of epithelial cells where it establishes tight binding between neighboring cells in adherens junctions. Like CD96, KLRG1 engages only the first Ig-like domain of its non-MHC ligand, forming an elongated structure whose overall length (∼190 Å) is remarkably similar to that of the CD96–necl-5 complex (Figure 1). The inhibitory functions of both CD96 and KLRG1 raise the activation threshold of NK cells, thereby attenuating cytotoxic responses and preventing damage to healthy tissues expressing normal levels of necl-5 and E-cadherin. Cancer cells regulate expression of these two cell–cell adhesion proteins in opposite directions in order to maximize tumor progression. The malignancy of epithelial tumors is often associated with downregulation of E-cadherin, which renders tumor cells invasive and metastatic (Jeanes et al., 2008Jeanes A. Gottardi C.J. Yap A.S. Cadherins and cancer: how does cadherin dysfunction promote tumor progression?.Oncogene. 2008; 27: 6920-6929Crossref PubMed Scopus (626) Google Scholar). However, loss of E-cadherin expression sensitizes tumor cells to NK-mediated cytotoxicity through KLRG1 (Chockley et al., 2018Chockley P.J. Chen J. Chen G. Beer D.G. Standiford T.J. Keshamouni V.G. Epithelial-mesenchymal transition leads to NK cell-mediated metastasis-specific immunosurveillance in lung cancer.J. Clin. Invest. 2018; 128: 1384-1396Crossref PubMed Scopus (71) Google Scholar). By contrast, as noted above, tumor cells upregulate necl-5 as a defense mechanism to escape elimination by NK cells expressing CD96 (Georgiev et al., 2018Georgiev H. Ravens I. Papadogianni G. Bernhardt G. Coming of age: CD96 emerges as modulator of immune responses.Front. Immunol. 2018; 9: 1072Crossref PubMed Scopus (56) Google Scholar). The CD96–necl-5 structure should accelerate the development of antibodies and potentially small molecules, targeting this interaction as a means to release the brakes on NK-mediated tumor cell killing. Structural Basis for CD96 Immune Receptor Recognition of Nectin-like Protein-5, CD155Deuss et al.StructureDecember 6, 2018In BriefDeuss et al. determined the structure of the immune receptor CD96 bound to its cognate ligand, CD155. This is a key interaction that facilitates immune evasion of tumor cells. Full-Text PDF Open Archive" @default.
• W2913939588 created "2019-02-21" @default.
• W2913939588 creator A5084093973 @default.
• W2913939588 creator A5086866774 @default.
• W2913939588 date "2019-02-01" @default.
• W2913939588 modified "2023-10-18" @default.
• W2913939588 title "How Natural Killer Cell Receptors Stick to Cell–Cell Adhesion Proteins" @default.
• W2913939588 cites W1964212105 @default.
• W2913939588 cites W2002725400 @default.
• W2913939588 cites W2082515849 @default.
• W2913939588 cites W2121158936 @default.
• W2913939588 cites W2128201178 @default.
• W2913939588 cites W2138687527 @default.
• W2913939588 cites W2616838116 @default.
• W2913939588 cites W2782792215 @default.
• W2913939588 cites W2801918257 @default.
• W2913939588 cites W2905064003 @default.
• W2913939588 doi "https://doi.org/10.1016/j.str.2019.01.007" @default.
• W2913939588 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30726753" @default.
• W2913939588 hasPublicationYear "2019" @default.
• W2913939588 type Work @default.
• W2913939588 sameAs 2913939588 @default.
• W2913939588 citedByCount "1" @default.
• W2913939588 countsByYear W29139395882019 @default.
• W2913939588 crossrefType "journal-article" @default.
• W2913939588 hasAuthorship W2913939588A5084093973 @default.
• W2913939588 hasAuthorship W2913939588A5086866774 @default.
• W2913939588 hasBestOaLocation W29139395881 @default.
• W2913939588 hasConcept C1491633281 @default.
• W2913939588 hasConcept C154317977 @default.
• W2913939588 hasConcept C170493617 @default.
• W2913939588 hasConcept C185592680 @default.
• W2913939588 hasConcept C202751555 @default.
• W2913939588 hasConcept C2778102761 @default.
• W2913939588 hasConcept C55493867 @default.
• W2913939588 hasConcept C85789140 @default.
• W2913939588 hasConcept C86803240 @default.
• W2913939588 hasConcept C95444343 @default.
• W2913939588 hasConceptScore W2913939588C1491633281 @default.
• W2913939588 hasConceptScore W2913939588C154317977 @default.
• W2913939588 hasConceptScore W2913939588C170493617 @default.
• W2913939588 hasConceptScore W2913939588C185592680 @default.
• W2913939588 hasConceptScore W2913939588C202751555 @default.
• W2913939588 hasConceptScore W2913939588C2778102761 @default.
• W2913939588 hasConceptScore W2913939588C55493867 @default.
• W2913939588 hasConceptScore W2913939588C85789140 @default.
• W2913939588 hasConceptScore W2913939588C86803240 @default.
• W2913939588 hasConceptScore W2913939588C95444343 @default.
• W2913939588 hasIssue "2" @default.
• W2913939588 hasLocation W29139395881 @default.
• W2913939588 hasLocation W29139395882 @default.
• W2913939588 hasOpenAccess W2913939588 @default.
• W2913939588 hasPrimaryLocation W29139395881 @default.
• W2913939588 hasRelatedWork W1494166566 @default.
• W2913939588 hasRelatedWork W152093826 @default.
• W2913939588 hasRelatedWork W1790932677 @default.
• W2913939588 hasRelatedWork W1993740514 @default.
• W2913939588 hasRelatedWork W2004997414 @default.
• W2913939588 hasRelatedWork W2017530429 @default.
• W2913939588 hasRelatedWork W2048760358 @default.
• W2913939588 hasRelatedWork W2059128760 @default.
• W2913939588 hasRelatedWork W2155429083 @default.
• W2913939588 hasRelatedWork W2416128704 @default.
• W2913939588 hasVolume "27" @default.
• W2913939588 isParatext "false" @default.
• W2913939588 isRetracted "false" @default.
• W2913939588 magId "2913939588" @default.
• W2913939588 workType "article" @default.