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Cited by 26S100 Proteins and AnnexinsProtein Structure and DynamicsParasitic Infections and Diagnostics

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Alpha-1 Giardin is an Annexin with Highly Unusual Calcium-Regulated Mechanisms

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Weeratunga, Saroja K., Osman, Asiah, Hu, Nien-Jen, Wang, Conan K., Mason, Lyndel, Svärd, Staffan, Hope, Greg, Jones, Malcolm K., Hofmann, Andreas·2012·Journal of Molecular Biology
DOI 10.1016/j.jmb.2012.06.041
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Abstract

Alpha-giardins constitute the annexin proteome (group E annexins) in the intestinal protozoan parasite Giardia and, as such, represent the evolutionary oldest eukaryotic annexins. The dominance of alpha-giardins in the cytoskeleton of Giardia with its greatly reduced actin content emphasises the importance of the alpha-giardins for the structural integrity of the parasite, which is particularly critical in the transformation stage between cyst and trophozoite. In this study, we report the crystal structures of the apo- and calcium-bound forms of α1-giardin, a protein localised to the plasma membrane of Giardia trophozoites that has recently been identified as a vaccine target. The calcium-bound crystal structure of α1-giardin revealed the presence of a type III site in the first repeat as known from other annexin structures, as well as a novel calcium binding site situated between repeats I and IV. By means of comparison, the crystal structures of three different alpha-giardins known to date indicate that these proteins engage different calcium coordination schemes, among each other, as well as compared to annexins of groups A-D. Evaluation of the calcium-dependent binding to acidic phosphoplipid membranes revealed that this process is not only mediated but also regulated by the environmental calcium concentration. Uniquely within the large family of annexins, α1-giardin disengages from the phospholipid membrane at high calcium concentrations possibly due to formation of a dimeric species. The observed behaviour is in line with changing calcium levels experienced by the parasite during excystation and may thus provide first insights into the molecular mechanisms underpinning the transformation and survival of the parasite in the host.

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  • Three distinct crystal structures of alpha-giardins (alpha-1, -11, and -14 giardins) have been solved, revealing the typical all alpha-helical annexin fold but with unusual calcium coordination schemes not known in other annexins.

    “Three distinct crystal structures of alpha-giardins (alpha-1, -11, and -14 giardins) have been solved, and this has revealed that they contain the typical all alpha-helical annexin fold but with unusual calcium coordination schemes not known in other annexins (9–11).”

    From Comparative Cell Biology and Evolution of Annexins in Diplomonads (2016) · cites this paper as [11]

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Cited by

Sorted by citations

  • Comparative Cell Biology and Evolution of Annexins in Diplomonads

    Einarsson, E., Ástvaldsson, Á., Hultenby, K., Andersson, J. O., Svärd, S. G., & Jerlström-Hultqvist, J. (2016) · mSphere · doi:10.1128/msphere.00032-15 · Cited by 15

    “These features give alpha-giardins unique properties; the alpha-1 giardin response to the Ca2 concentration is highly unusual, with abrogated binding to acidic phospholipids at high concentrations, a feature that might be coupled to environmental sensing early during host colonization (11).”
    BackgroundSelf-citation

Metadata

Authors
Weeratunga, S. K., Osman, A., Hu, N.-J., Wang, C. K., Mason, L., Svärd, S., Hope, G., Jones, M. K., & Hofmann, A.
Affiliations
  • Griffith University (AU)
  • Imperial College London (GB)
  • Uppsala University (SE)
  • The University of Queensland (AU)
Corresponding author
Hofmann, Andreas
ORCID
Venue
Journal of Molecular Biology
Publisher
Elsevier BV
Published
2012-10
Volume
423
Issue
2
Pages
169-181
ISSN
0022-2836 (ISSN-L)
DOI
10.1016/j.jmb.2012.06.041
OpenAlex
W2043129641
Cited by
26
References
3
Citations by year
2026: 3 · 2025: 1 · 2024: 1 · 2023: 3 · 2020: 1 · 2019: 4 · 2018: 1 · 2017: 2 · 2016: 5 · 2015: 1 · 2014: 2 · 2013: 2
FWCI
0.64
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Journal of Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Griffith Research Online (submittedVersion)
Funders
  • Rebecca Cooper Foundation
  • James N. Kirby Foundation
  • National Health and Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Immunology and Microbiology › Parasitology › Parasitic Infections and Diagnostics
Keywords
Giardia, annexins, calcium binding, crystal structure, membrane binding, protein dimerization, excystation, trophozoites, cysts, vaccine targets
MeSH terms
Animals, Binding Sites, Calcium, Cytoskeletal Proteins, Glycosaminoglycans, Membranes, Artificial, Models, Molecular, Molecular Sequence Data, Phospholipids, Protozoan Proteins, Giardia lamblia, Crystallography, X-Ray

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