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Structure of the C-terminal domain from Trypanosoma brucei Variant Surface Glycoprotein MITat1.2
Structural highlights
FunctionVSM2_TRYBB VSG forms a coat on the surface of the parasite. The trypanosome evades the immune response of the host by expressing a series of antigenically distinct VSGs from an estimated 1000 VSG genes. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. Structure of the C-terminal domain from Trypanosoma brucei variant surface glycoprotein MITat1.2.,Chattopadhyay A, Jones NG, Nietlispach D, Nielsen PR, Voorheis HP, Mott HR, Carrington M J Biol Chem. 2005 Feb 25;280(8):7228-35. Epub 2004 Nov 22. PMID:15557330[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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