title: Structure of a heterophilic adhesion complex between the human CD2 and CD58 (LFA-3) counterreceptors.
abstract: Interaction between CD2 and its counterreceptor, CD58 (LFA-3), on opposing cells optimizes immune recognition, facilitating contacts between helper T lymphocytes and antigen-presenting cells as well as between cytolytic effectors and target cells. Here, we report the crystal structure of the heterophilic adhesion complex between the amino-terminal domains of human CD2 and CD58. A strikingly asymmetric, orthogonal, face-to-face interaction involving the major beta sheets of the respective immunoglobulin-like domains with poor shape complementarity is revealed. In the virtual absence of hydrophobic forces, interdigitating charged amino acid side chains form hydrogen bonds and salt links at the interface (approximately 1200 A2), imparting a high degree of specificity albeit with low affinity (K(D) of approximately microM). These features explain CD2-CD58 dynamic binding, offering insights into interactions of related immunoglobulin superfamily receptors.
authors.affiliation: Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. jwang@red.dfci.harvard.edu
authors.forename: J H
authors.initials: JH
authors.lastname: Wang
authors.forename: A
authors.initials: A
authors.lastname: Smolyar
authors.forename: K
authors.initials: K
authors.lastname: Tan
authors.forename: J H
authors.initials: JH
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Kim
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Sun
authors.forename: G
authors.initials: G
authors.lastname: Wagner
authors.forename: E L
authors.initials: EL
authors.lastname: Reinherz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018801:CD2 Antigens / Q000737:chemistry* / Q000378:metabolism; D018968:CD58 Antigens / Q000737:chemistry* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000737:chemistry; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D051381:Rats; D017386:Sequence Homology, Amino Acid
chemical_list: D018801:CD2 Antigens; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules