Determination of the Disulfide Bonds within a B Domain Variant Surface Glycoprotein from Trypanosoma congolense

Bussler, H; Linder, Monica; Linder, Dietmar; Reinwald, E.

doi:10.1074/jbc.273.49.32582

Cited by 15 publications

(7 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These five VSGs all have type B N-terminal domains and although there is firm evidence that they adopt a similar tertiary structure to type A VSGs [25] they are less well characterized. The analysis showed that the differences between the members of each triplet were more evenly distributed throughout the primary structure than for the Buteba 4 family.…”

Section: Resultsmentioning

confidence: 99%

Variant Surface Glycoprotein gene repertoires in Trypanosoma brucei have diverged to become strain-specific

et al. 2007

View full text Add to dashboard Cite

Background: In a mammalian host, the cell surface of African trypanosomes is protected by a monolayer of a single variant surface glycoprotein (VSG). The VSG is central to antigenic variation; one VSG gene is expressed at any one time and there is a low frequency stochastic switch to expression of a different VSG gene. The genome of Trypanosoma brucei contains a repertoire of > 1000 VSG sequences. The degree of conservation of the genomic VSG repertoire in different strains has not been investigated in detail.

show abstract

Section: Resultsmentioning

confidence: 99%

Variant Surface Glycoprotein gene repertoires in Trypanosoma brucei have diverged to become strain-specific

et al. 2007

View full text Add to dashboard Cite

show abstract

“…The VSG N-terminal domain has 350 -400 residues, which are followed by one or two C-terminal domains of 30 -70 residues each. Less is known about T. congolense and T. vivax VSGs; they are somewhat smaller, 45-50 kDa, and have a single domain that is similar to the T. brucei VSG N-terminal domain (4). VSGs are dimeric (5,6) and are attached to the plasma membrane via a covalent linkage from the C-terminal carboxyl group to a glycosylphosphatidylinositol anchor (7).…”

mentioning

confidence: 99%

Structure of the C-terminal Domain from Trypanosoma brucei Variant Surface Glycoprotein MITat1.2

Chattopadhyay

Jones

Nietlispach

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

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 ␣-helix followed by a single turn of 3 10 -helix and connected by a short loop to a small anti-parallel ␤-sheet and then a longer ␣-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 ␣-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.African trypanosomes have evolved a complex system of antigenic variation that facilitates the long term survival of a population in a mammalian host (see Ref. 1 for a recent review). The entire cell surface is covered with a densely packed monolayer of a single polypeptide, the variant surface glycoprotein (VSG), 1 which protects other cell surface components from effectors of the host immune system. The VSG is also the mediator of antigenic variation. At any time, only a single VSG gene is expressed, and antigenic variation results from a low frequency, stochastic event that causes a switch to the expression of a different VSG gene. During the course of an infection, there are successive clonal expansions of trypanosomes, each expressing an antigenically novel VSG.In Trypanosoma brucei and the closely related species T. evansi and T. equiperdum, each VSG monomer has a molecular mass of 45-55 kDa and is made up of two or three domains (2, 3). The VSG N-terminal domain has 350 -400 residues, which are followed by one or two C-terminal domains of 30 -70 residues each. Less is known about T. congolense and T. vivax VSGs; they are somewhat smaller, 45-50 kDa, and have a single domain that is similar to the T. brucei VSG N-terminal domain (4). VSGs are dimeric (5, 6) and are attached to the plasma membrane via a covalent linkage from the C-terminal carboxyl group to a glycosylphosphatidylinositol anchor (7).VSGs that are successively expressed by an infecting population are ant...

show abstract

“…4. Dmax was determined from the pair distance distribution function P(r) with the program GNOM (Bussler et al, 1998;Svergun, 1992). In determining Dmax, GNOM gives a "total estimate", which identifies common artifacts encountered by the GNOM method.…”

Section: Sec-saxs Experiments Were Performed At the Biocat Beamline 1mentioning

confidence: 99%

Structural assembly of the human Miro1/2 GTPases based on the crystal structure of the N-terminal GTPase domain

Smith

Focia

Chakravarthy

et al. 2019

Preprint

View full text Add to dashboard Cite

PDB reference: Crystal structure of the human Miro1 N-terminal GTPase bound to GTP, 6D71 Abstract Dysfunction in mitochondrial dynamics is believed to contribute to a host of neurological disorders and has recently been implicated in cancer metastasis. The outer mitochondrial membrane adapter protein Miro functions in the regulation of mitochondrial mobility and degradation, however, the structural basis for its roles in mitochondrial regulation remain unknown. Here, we report a 1.7Å crystal structure of Nterminal GTPase domain (nGTPase) of human Miro1 bound unexpectedly to GTP, thereby revealing a non-catalytic configuration of the putative GTPase active site. We identify two conserved surfaces of the nGTPase, the "SELFYY" and "ITIP" motifs, that are potentially positioned to mediate dimerization or interaction with binding partners. Additionally, we report small angle X-ray scattering (SAXS) data obtained from the intact soluble HsMiro1 and its paralog HsMiro2. Taken together, the data allow modeling of a crescent-shaped assembly of the full-length soluble domain of HsMiro1/2.

show abstract

Determination of the Disulfide Bonds within a B Domain Variant Surface Glycoprotein from Trypanosoma congolense

Cited by 15 publications

References 27 publications

Variant Surface Glycoprotein gene repertoires in Trypanosoma brucei have diverged to become strain-specific

Variant Surface Glycoprotein gene repertoires in Trypanosoma brucei have diverged to become strain-specific

Structure of the C-terminal Domain from Trypanosoma brucei Variant Surface Glycoprotein MITat1.2

Structural assembly of the human Miro1/2 GTPases based on the crystal structure of the N-terminal GTPase domain

Contact Info

Product

Resources

About