title: Structural and functional analysis of integrin alpha2I domain interaction with echovirus 1.
abstract: Integrins are cell surface receptors for several microbial pathogens including echovirus 1 (EV1), a picornavirus. Cryo-electron microscopy revealed that the functional domain (alpha(2)I) of human alpha(2)beta(1) integrin binds to a surface depression on the EV1 capsid. This three-dimensional structure of EV1 bound to alpha(2)I domain provides the first structural details of an integrin interacting with a picornavirus. The model indicates that alpha(2)beta(1) integrin cannot simultaneously bind both EV1 and the physiological ligand collagen. Compared with collagen binding to the alpha(2)I domain, the virus binds with a 10-fold higher affinity but in vitro uncoating of EV1 was not observed as a result of attachment of alpha(2)I. A molecular model, constructed on the basis of the EV1-integrin complex, shows that multiple alpha(2)beta(1) heterodimers can bind at adjacent sites around the virus 5-fold symmetry axes without steric hindrance. In agreement with this, virus attachment to alpha(2)beta(1) integrin on the cell surface was found to result in integrin clustering, which can give rise to signaling and facilitate the initiation of the viral entry process that takes place via caveolae-mediated endocytosis.
authors.affiliation: Department of Biosciences, Karolinska Institute, 14157 Stockholm, Sweden.
authors.forename: Li
authors.initials: L
authors.lastname: Xing
authors.forename: Mikko
authors.initials: M
authors.lastname: Huhtala
authors.forename: Vilja
authors.initials: V
authors.lastname: Pietiäinen
authors.forename: Jarmo
authors.initials: J
authors.lastname: Käpylä
authors.forename: Kirsi
authors.initials: K
authors.lastname: Vuorinen
authors.forename: Varpu
authors.initials: V
authors.lastname: Marjomäki
authors.forename: Jyrki
authors.initials: J
authors.lastname: Heino
authors.forename: Mark S
authors.initials: MS
authors.lastname: Johnson
authors.forename: Timo
authors.initials: T
authors.lastname: Hyypiä
authors.forename: R Holland
authors.initials: RH
authors.lastname: Cheng
mesh_terms: D002213:Capsid / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D020285:Cryoelectron Microscopy; D029822:Enterovirus B, Human / Q000502:physiology* / Q000648:ultrastructure; D004769:Enterovirus Infections / Q000503:physiopathology; D006801:Humans; D039421:Integrin alpha2 / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008855:Microscopy, Electron, Scanning; D011487:Protein Conformation; D011991:Receptors, Virus / Q000502:physiology
chemical_list: D039421:Integrin alpha2; D011991:Receptors, Virus