title: Fibronectin type III domains engineered to bind CD40L: cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of two complexes.
abstract: Tn3 proteins are a novel class of binding molecules based on the third fibronectin type III domain of human tenascin C. Target-specific Tn3 proteins are selected from combinatorial libraries in which three surface-exposed loops have been diversified. Here, the cocrystallization of two different Tn3 proteins in complex with CD40L, a therapeutic target for immunological disease, is reported. These crystal structures are the first to be reported of Tn3 proteins and will help to reveal how these engineered molecules achieve specific recognition of a cognate target.
authors.affiliation: Department of Antibody Discovery and Protein Engineering, MedImmune, One MedImmune Way, Gaithersburg, MD 20878, USA. oganesyanv@medimmune.com
authors.forename: Vaheh
authors.initials: V
authors.lastname: Oganesyan
authors.forename: Andrew
authors.initials: A
authors.lastname: Ferguson
authors.forename: Luba
authors.initials: L
authors.lastname: Grinberg
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Sandrina
authors.initials: S
authors.lastname: Phipps
authors.forename: Benoy
authors.initials: B
authors.lastname: Chacko
authors.forename: Stacey
authors.initials: S
authors.lastname: Drabic
authors.forename: Thomas
authors.initials: T
authors.lastname: Thisted
authors.forename: Manuel
authors.initials: M
authors.lastname: Baca
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D023201:CD40 Ligand / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics; D005353:Fibronectins / Q000737:chemistry* / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D016415:Sequence Alignment
chemical_list: D005353:Fibronectins; D019151:Peptide Library; D010455:Peptides; D011994:Recombinant Proteins; D023201:CD40 Ligand
keywords: CD40L; fibronectin type III domains