Observed octameric assembly of a Plasmodium yoelii peroxiredoxin can be explained by the replacement of native “ball‐and‐socket” interacting residues by an affinity tag

Peroxiredoxins (Prxs) are ubiquitous and efficient antioxidant enzymes crucial for redox homeostasis in most organisms, and are of special importance for disease‐causing parasites that must protect themselves against the oxidative weapons of the human immune system. Here, we describe reanalyses of c...

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Bibliographic Details
Published in:Protein science 2013-10, Vol.22 (10), p.1445-1452
Main Authors: Gretes, Michael C., Karplus, P. Andrew
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Amino Acids - chemistry
Amino Acids - metabolism
Antigens
Catalytic Domain
Crystal structure
Crystallography, X-Ray
dimer interface
Enzymes
For the Record
Genetic Variation
Humans
hyperoxidation
malaria
Malaria - parasitology
Models, Molecular
Molecular Sequence Data
peroxidase
Peroxiredoxins - chemistry
Peroxiredoxins - metabolism
Plasmodium yoelii
Plasmodium yoelii - enzymology
Protein Multimerization
protein structure
Protein Structure, Quaternary
Protozoan Proteins - chemistry
Protozoan Proteins - metabolism
radiation damage
structural genomics
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Summary:Peroxiredoxins (Prxs) are ubiquitous and efficient antioxidant enzymes crucial for redox homeostasis in most organisms, and are of special importance for disease‐causing parasites that must protect themselves against the oxidative weapons of the human immune system. Here, we describe reanalyses of crystal structures of two Prxs from malaria parasites. In addition to producing improved structures, we provide normalizing explanations for features that had been noted as unusual in the original report of these structures (Qiu et al., BMC Struct Biol 2012;12:2). Most importantly, we provide evidence that the unusual octameric assembly seen for Plasmodium yoelii Prx1a is not physiologically relevant, but arises because the structure is not of authentic P. yoelii Prx1a, but a variant we designate PyPrx1aN* that has seven native N‐terminal residues replaced by an affinity tag. This N‐terminal modification disrupts a previously unrecognized, hydrophobic “ball‐and‐socket” interaction conserved at the B‐type dimer interface of Prx1 subfamily enzymes, and is accommodated by a fascinating two‐residue “β‐slip” type register shift in the β‐strand association at a dimer interface. The resulting change in the geometry of the dimer provides a simple explanation for octamer formation. This study illustrates how substantive impacts can occur in protein variants in which native residues have been altered. Interactive Figure 2
ISSN:0961-8368
1469-896X
DOI:10.1002/pro.2328