Linked Life Data

15157084

Source:http://linkedlifedata.com/resource/pubmed/id/15157084

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2004-5-25
pubmed:databankReference
pubmed:abstractText
Understanding the factors governing the thermal stability of proteins and correlating them to the sequence and structure is a complex and multiple problem that can nevertheless provide important information on the molecular forces involved in protein folding. Here, we have carried out a comparative genomic study to analyze the effects that different intrinsic and environmental factors have on the thermal stability of frataxins, a family of small mitochondrial iron-binding proteins found in organisms ranging from bacteria to humans. Low expression of frataxin in humans causes Friedreich's ataxia, an autosomal recessive neurodegenerative disease. The human, yeast, and bacterial orthologues were selected as representatives of different evolutionary steps. Although sharing high sequence homology and the same three-dimensional fold, the three proteins have a large variability in their thermal stabilities. Whereas bacterial and human frataxins are thermally stable, well-behaved proteins, under the same conditions yeast frataxin exists in solution as an unstable species with apprechable tracts in a conformational exchange. By designing suitable mutants, we show and justify structurally that the length of the C-terminus is an important intrinsic factor that directly correlates with the thermal stabilities of the three proteins. Thermal stability is also gained by the addition of Fe(2+). This effect, however, is not uniform for the three orthologues nor highly specific for iron: a similar albeit weaker stabilization is observed with other mono- and divalent cations. We discuss the implications that our findings have for the role of frataxins as iron-binding proteins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6511-8
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15157084-Amino Acid Sequence, pubmed-meshheading:15157084-Bacterial Proteins, pubmed-meshheading:15157084-Circular Dichroism, pubmed-meshheading:15157084-Escherichia coli Proteins, pubmed-meshheading:15157084-Humans, pubmed-meshheading:15157084-Iron, pubmed-meshheading:15157084-Iron-Binding Proteins, pubmed-meshheading:15157084-Magnetic Resonance Spectroscopy, pubmed-meshheading:15157084-Models, Molecular, pubmed-meshheading:15157084-Molecular Sequence Data, pubmed-meshheading:15157084-Mutation, pubmed-meshheading:15157084-Protein Conformation, pubmed-meshheading:15157084-Saccharomyces cerevisiae Proteins, pubmed-meshheading:15157084-Sequence Homology, Amino Acid, pubmed-meshheading:15157084-Structural Homology, Protein, pubmed-meshheading:15157084-Structure-Activity Relationship, pubmed-meshheading:15157084-Thermodynamics
pubmed:year
2004
pubmed:articleTitle
The factors governing the thermal stability of frataxin orthologues: how to increase a protein's stability.
pubmed:affiliation
National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't