title: Nectin family of cell-adhesion molecules: structural and molecular aspects of function and specificity.
abstract: Cell-cell adhesive processes are central to the physiology of multicellular organisms. A number of cell surface molecules contribute to cell-cell adhesion, and the dysfunction of adhesive processes underlies numerous developmental defects and inherited diseases. The nectins, a family of four immunoglobulin superfamily members (nectin-1 to -4), interact through their extracellular domains to support cell-cell adhesion. While both homophilic and heterophilic interactions among the nectins are implicated in cell-cell adhesion, cell-based and biochemical studies suggest heterophilic interactions are stronger than homophilic interactions and control a range of physiological processes. In addition to interactions within the nectin family, heterophilic associations with nectin-like molecules, immune receptors, and viral glycoproteins support a wide range of biological functions, including immune modulation, cancer progression, host-pathogen interactions and immune evasion. We review current structural and molecular knowledge of nectin recognition processes, with a focus on the biochemical and biophysical determinants of affinity and selectivity that drive distinct nectin associations. These proteins and interactions are discussed as potential targets for immunotherapy.
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA, dibyendu.samanta@einstein.yu.edu.
authors.forename: Dibyendu
authors.initials: D
authors.lastname: Samanta
authors.forename: Steven C
authors.initials: SC
authors.lastname: Almo
mesh_terms: D015820:Cadherins / Q000737:chemistry / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D000075983:Nectins; D054730:Protein Interaction Domains and Motifs; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C000619010:NECTIN1 protein, human; D000075983:Nectins; D020033:Protein Isoforms