title: Crystal structures of an ICAM-5 ectodomain fragment show electrostatic-based homophilic adhesions.
abstract: Intercellular cell adhesion molecule-5 (ICAM-5) is a member of the ICAM subfamily that is exclusively expressed in the telencephalon region of the brain. The crystal structure of the four most N-terminal glycosylated domains (D1-D4) of ICAM-5 was determined in three different space groups and the D1-D5 fragment was modelled. The structures showed a curved molecule with two pronounced interdomain bends between D2 and D3 and between D3 and D4, as well as some interdomain flexibility. In contrast to ICAM-1, ICAM-5 has patches of positive and negative electrostatic charge at D1-D2 and at D3-D5, respectively. ICAM-5 can mediate homotypic interactions. In the crystals, several charge-based intermolecular interactions between the N-terminal and C-terminal moieties of the ICAM-5 molecules were observed, which defined an interacting surface in the D1-D4 fragment. One of the crystal lattices has a molecular assembly that could represent the homophilic ICAM-5 cell adhesion complex in neurons.
authors.affiliation: Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Darwin 3,, 28049 Madrid, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Recacha
authors.affiliation: Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Darwin 3,, 28049 Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Jiménez
authors.affiliation: Neuroscience Center, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Li
authors.initials: L
authors.lastname: Tian
authors.affiliation: Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Darwin 3,, 28049 Madrid, Spain.
authors.forename: Román
authors.initials: R
authors.lastname: Barredo
authors.affiliation: Division of Biochemistry and Biotechnology, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Carl G
authors.initials: CG
authors.lastname: Gahmberg
authors.affiliation: Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Darwin 3,, 28049 Madrid, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Casasnovas
mesh_terms: D000595:Amino Acid Sequence; D015815:Cell Adhesion Molecules / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
chemical_list: D015815:Cell Adhesion Molecules; C086747:ICAM5 protein, human; D009419:Nerve Tissue Proteins
keywords: ICAM-5; cell adhesion; immunoglobulin superfamily; neuron