title: Crystallization and preliminary X-ray diffraction analysis of the interleukin-3 alpha receptor bound to the Fab fragment of antibody CSL362.
abstract: Interleukin-3 (IL-3) is a member of the beta common family of cytokines that regulate multiple functions of myeloid cells. The IL-3 receptor-specific alpha subunit (IL3Rα) is overexpressed on stem cells/progenitor cells of patients with acute myeloid leukaemia, where elevated receptor expression correlates clinically with a reduced patient survival rate. The monoclonal antibody (MAb) CSL362 is a humanized MAb derived from the murine MAb 7G3, originally identified for its ability to specifically recognize the human IL-3 receptor and for blocking the signalling of IL-3 in myeloid and endothelial cells. In order to elucidate the molecular mechanism of CSL362 antagonism, a preliminary structure of human IL3Rα in complex with the MAb CSL362 has been determined.
authors.affiliation: Australian Cancer Research Foundation Rational Drug Discovery Centre and Biota Structural Biology Laboratory, St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Broughton
authors.affiliation: Division of Human Immunology, The Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, Australia.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Hercus
authors.affiliation: Australian Cancer Research Foundation Rational Drug Discovery Centre and Biota Structural Biology Laboratory, St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Nero
authors.affiliation: Australian Cancer Research Foundation Rational Drug Discovery Centre and Biota Structural Biology Laboratory, St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
authors.forename: Urmi
authors.initials: U
authors.lastname: Dhagat
authors.affiliation: CSL Limited, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Owczarek
authors.affiliation: CSL Limited, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Hardy
authors.affiliation: CSL Limited, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Fabri
authors.affiliation: CSL Limited, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Pierre D
authors.initials: PD
authors.lastname: Scotney
authors.affiliation: CSL Limited, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Nash
authors.affiliation: CSL Limited, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wilson
authors.affiliation: Division of Human Immunology, The Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, Australia.
authors.forename: Angel F
authors.initials: AF
authors.lastname: Lopez
authors.affiliation: Australian Cancer Research Foundation Rational Drug Discovery Centre and Biota Structural Biology Laboratory, St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Parker
mesh_terms: D000595:Amino Acid Sequence; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry*; D003460:Crystallization; D006801:Humans; D053650:Interleukin-3 Receptor alpha Subunit / Q000737:chemistry*; D008969:Molecular Sequence Data; D011485:Protein Binding; D014961:X-Ray Diffraction
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit
keywords: IL-3 receptor-specific alpha subunit; cytokines; interleukin-3