title: Structure of the C-terminal domain from Trypanosoma brucei variant surface glycoprotein MITat1.2.
abstract: The variant surface glycoprotein (VSG) of African trypanosomes has a structural role in protecting other cell surface proteins from effector molecules of the mammalian immune system and also undergoes antigenic variation necessary for a persistent infection in a host. Here we have reported the solution structure of a VSG type 2 C-terminal domain from MITat1.2, completing the first structure of both domains of a VSG. The isolated C-terminal domain is a monomer in solution and forms a novel fold, which commences with a short alpha-helix followed by a single turn of 3(10)-helix and connected by a short loop to a small anti-parallel beta-sheet and then a longer alpha-helix at the C terminus. This compact domain is flanked by two unstructured regions. The structured part of the domain contains 42 residues, and the core comprises 2 disulfide bonds and 2 hydrophobic residues. These cysteines and hydrophobic residues are conserved in other VSGs, and we have modeled the structures of two further VSG C-terminal domains using the structure of MITat1.2. The models suggest that the overall structure of the core is conserved in the different VSGs but that the C-terminal alpha-helix is of variable length and depends on the presence of charged residues. The results provided evidence for a conserved tertiary structure for all the type 2 VSG C-terminal domains, indicated that VSG dimers form through interactions between N-terminal domains, and showed that the selection pressure for sequence variation within a conserved tertiary structure acts on the whole of the VSG molecule.
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom.
authors.forename: Anasuya
authors.initials: A
authors.lastname: Chattopadhyay
authors.forename: Nicola G
authors.initials: NG
authors.lastname: Jones
authors.forename: Daniel
authors.initials: D
authors.lastname: Nietlispach
authors.forename: Peter R
authors.initials: PR
authors.lastname: Nielsen
authors.forename: H Paul
authors.initials: HP
authors.lastname: Voorheis
authors.forename: Helen R
authors.initials: HR
authors.lastname: Mott
authors.forename: Mark
authors.initials: M
authors.lastname: Carrington
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003198:Computer Simulation; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D017434:Protein Structure, Tertiary; D012641:Selection, Genetic; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D014346:Trypanosoma brucei brucei / Q000737:chemistry*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000737:chemistry*
chemical_list: D014643:Variant Surface Glycoproteins, Trypanosoma