Advanced

Oligomerization Propensity and Flexibility of Yeast Frataxin Studied by X-ray Crystallography and Small-Angle X-ray Scattering.

Söderberg, Christopher LU ; Shkumatov, Alexander V; Rajan, Sreekanth LU ; Gakh, Oleksandr; Svergun, Dmitri I; Isaya, Grazia and Al-Karadaghi, Salam LU (2011) In Journal of Molecular Biology 414(5). p.783-797
Abstract
Frataxin is a mitochondrial protein with a central role in iron homeostasis. Defects in frataxin function lead to Friedreich's ataxia, a progressive neurodegenerative disease with childhood onset. The function of frataxin has been shown to be closely associated with its ability to form oligomeric species; however, the factors controlling oligomerization and the types of oligomers present in solution are a matter of debate. Using small-angle X-ray scattering, we found that Co(2+), glycerol, and a single amino acid substitution at the N-terminus, Y73A, facilitate oligomerization of yeast frataxin, resulting in a dynamic equilibrium between monomers, dimers, trimers, hexamers, and higher-order oligomers. Using X-ray crystallography, we found... (More)
Frataxin is a mitochondrial protein with a central role in iron homeostasis. Defects in frataxin function lead to Friedreich's ataxia, a progressive neurodegenerative disease with childhood onset. The function of frataxin has been shown to be closely associated with its ability to form oligomeric species; however, the factors controlling oligomerization and the types of oligomers present in solution are a matter of debate. Using small-angle X-ray scattering, we found that Co(2+), glycerol, and a single amino acid substitution at the N-terminus, Y73A, facilitate oligomerization of yeast frataxin, resulting in a dynamic equilibrium between monomers, dimers, trimers, hexamers, and higher-order oligomers. Using X-ray crystallography, we found that Co(2+) binds inside the channel at the 3-fold axis of the trimer, which suggests that the metal has an oligomer-stabilizing role. The results reveal the types of oligomers present in solution and support our earlier suggestions that the trimer is the main building block of yeast frataxin oligomers. They also indicate that different mechanisms may control oligomer stability and oligomerization in vivo. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Molecular Biology
volume
414
issue
5
pages
783 - 797
publisher
Elsevier
external identifiers
  • wos:000298526800011
  • pmid:22051511
  • scopus:82555187015
ISSN
1089-8638
DOI
10.1016/j.jmb.2011.10.034
language
English
LU publication?
yes
id
23e8a5c9-335c-4f15-b8ec-579dce8afc74 (old id 2221180)
date added to LUP
2011-12-13 17:09:29
date last changed
2017-09-24 03:49:20
@article{23e8a5c9-335c-4f15-b8ec-579dce8afc74,
  abstract     = {Frataxin is a mitochondrial protein with a central role in iron homeostasis. Defects in frataxin function lead to Friedreich's ataxia, a progressive neurodegenerative disease with childhood onset. The function of frataxin has been shown to be closely associated with its ability to form oligomeric species; however, the factors controlling oligomerization and the types of oligomers present in solution are a matter of debate. Using small-angle X-ray scattering, we found that Co(2+), glycerol, and a single amino acid substitution at the N-terminus, Y73A, facilitate oligomerization of yeast frataxin, resulting in a dynamic equilibrium between monomers, dimers, trimers, hexamers, and higher-order oligomers. Using X-ray crystallography, we found that Co(2+) binds inside the channel at the 3-fold axis of the trimer, which suggests that the metal has an oligomer-stabilizing role. The results reveal the types of oligomers present in solution and support our earlier suggestions that the trimer is the main building block of yeast frataxin oligomers. They also indicate that different mechanisms may control oligomer stability and oligomerization in vivo.},
  author       = {Söderberg, Christopher and Shkumatov, Alexander V and Rajan, Sreekanth and Gakh, Oleksandr and Svergun, Dmitri I and Isaya, Grazia and Al-Karadaghi, Salam},
  issn         = {1089-8638},
  language     = {eng},
  number       = {5},
  pages        = {783--797},
  publisher    = {Elsevier},
  series       = {Journal of Molecular Biology},
  title        = {Oligomerization Propensity and Flexibility of Yeast Frataxin Studied by X-ray Crystallography and Small-Angle X-ray Scattering.},
  url          = {http://dx.doi.org/10.1016/j.jmb.2011.10.034},
  volume       = {414},
  year         = {2011},
}