title: Analysis of the solution structure of human interleukin-4 determined by heteronuclear three-dimensional nuclear magnetic resonance techniques.
abstract: Human interleukin-4 (IL-4) is a member of the family of haemopoietic cytokines that modulate cell proliferation and differentiation within the immune system. It has a four-helix-bundle structure, and possesses a high degree of mobility in certain regions, notably in the two long loops running the length of the bundle in its up-up-down-down topology. Information from a variety of three-dimensional heteronuclear NMR experiments, including chemical shifts, coupling constants and NOE data, is analysed in terms of the solution structure of IL-4. In addition, structure calculations with and without specific restraints such as hydrogen bond location or torsion angle restrictions are compared in the light of the dynamic behaviour of the polypeptide chain. Particular emphasis is placed on defining the lengths and positions of secondary structure elements, and on the likely structural preferences within the less well ordered loop regions. The overall topology of IL-4 is compared with those defined in recent structure determinations of related proteins. This analysis is combined with recent mutagenesis data to propose a possible mode of interaction of IL-4 with its receptor.
authors.affiliation: Oxford Centre for Molecular Sciences, University of Oxford, UK.
authors.forename: C
authors.initials: C
authors.lastname: Redfield
authors.forename: L J
authors.initials: LJ
authors.lastname: Smith
authors.forename: J
authors.initials: J
authors.lastname: Boyd
authors.forename: G M
authors.initials: GM
authors.lastname: Lawrence
authors.forename: R G
authors.initials: RG
authors.lastname: Edwards
authors.forename: C J
authors.initials: CJ
authors.lastname: Gershater
authors.forename: R A
authors.initials: RA
authors.lastname: Smith
authors.forename: C M
authors.initials: CM
authors.lastname: Dobson
mesh_terms: D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D015847:Interleukin-4 / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D017433:Protein Structure, Secondary
chemical_list: D015847:Interleukin-4