Linked Life Data

18440022

Source:http://linkedlifedata.com/resource/pubmed/id/18440022

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-5-9
pubmed:abstractText
Merozoite surface protein 2 (MSP2), one of the most abundant proteins on the surface of the merozoite stage of Plasmodium falciparum, is a potential component of a malaria vaccine, having shown some efficacy in a clinical trial in Papua New Guinea. MSP2 is a GPI-anchored protein consisting of conserved N- and C-terminal domains and a variable central region. Previous studies have shown that it is an intrinsically unstructured protein with a high propensity for fibril formation, in which the conserved N-terminal domain has a key role. Secondary structure predictions suggest that MSP2 contains long stretches of random coil with very little alpha-helix or beta-strand. Circular dichroism spectroscopy confirms this prediction under physiological conditions (pH 7.4) and in more acidic solutions (pH 6.2 and 3.4). Pulsed field gradient NMR diffusion measurements showed that MSP2 under physiological conditions has a large effective hydrodynamic radius consistent with an intrinsic pre-molten globule state, as defined by Uversky. This was supported by sedimentation velocity studies in the analytical ultracentrifuge. NMR resonance assignments have been obtained for FC27 MSP2, allowing the residual secondary structure and backbone dynamics to be defined. There is some motional restriction in the conserved C-terminal region in the vicinity of an intramolecular disulfide bond. Two other regions show motional restrictions, both of which display helical structure propensities. One of these helical regions is within the conserved N-terminal domain, which adopts essentially the same conformation in full-length MSP2 as in corresponding peptide fragments. We see no evidence of long-range interactions in the full-length protein. MSP2 associates with lipid micelles, but predominantly through the N-terminal region rather than the C terminus, which is GPI-anchored to the membrane in the parasite.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1089-8638
pubmed:author
pubmed:issnType
Electronic
pubmed:day
23
pubmed:volume
379
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
105-21
pubmed:meshHeading
pubmed-meshheading:18440022-Amino Acid Sequence, pubmed-meshheading:18440022-Animals, pubmed-meshheading:18440022-Antigens, Protozoan, pubmed-meshheading:18440022-Circular Dichroism, pubmed-meshheading:18440022-Disulfides, pubmed-meshheading:18440022-Lipids, pubmed-meshheading:18440022-Micelles, pubmed-meshheading:18440022-Molecular Sequence Data, pubmed-meshheading:18440022-Nuclear Magnetic Resonance, Biomolecular, pubmed-meshheading:18440022-Oxidation-Reduction, pubmed-meshheading:18440022-Peptides, pubmed-meshheading:18440022-Phosphorylcholine, pubmed-meshheading:18440022-Plasmodium falciparum, pubmed-meshheading:18440022-Protein Structure, Secondary, pubmed-meshheading:18440022-Protozoan Proteins, pubmed-meshheading:18440022-Sequence Analysis, Protein, pubmed-meshheading:18440022-Solutions, pubmed-meshheading:18440022-Ultracentrifugation
pubmed:year
2008
pubmed:articleTitle
Solution conformation, backbone dynamics and lipid interactions of the intrinsically unstructured malaria surface protein MSP2.
pubmed:affiliation
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville 3050, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural