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Apo and calcium-bound crystal structures of cytoskeletal protein alpha-14 giardin (annexin E1) from the intestinal protozoan parasite Giardia lamblia.

Pathuri P, Nguyen ET, Ozorowski G, Svärd SG, Luecke H
J Mol Biol 385 1098-112 (2009)
Related entries: 3chk, 3chl

Cited: 8 times
EuropePMC logo PMID: 19046974

Abstract

Alpha-14 giardin (annexin E1), a member of the alpha giardin family of annexins, has been shown to localize to the flagella of the intestinal protozoan parasite Giardia lamblia. Alpha giardins show a common ancestry with the annexins, a family of proteins most of which bind to phospholipids and cellular membranes in a Ca(2+)-dependent manner and are implicated in numerous membrane-related processes including cytoskeletal rearrangements and membrane organization. It has been proposed that alpha-14 giardin may play a significant role during the cytoskeletal rearrangement during differentiation of Giardia. To gain a better understanding of alpha-14 giardin's mode of action and its biological role, we have determined the three-dimensional structure of alpha-14 giardin and its phospholipid-binding properties. Here, we report the apo crystal structure of alpha-14 giardin determined in two different crystal forms as well as the Ca(2+)-bound crystal structure of alpha-14 giardin, refined to 1.9, 1.6 and 1.65 A, respectively. Although the overall fold of alpha-14 giardin is similar to that of alpha-11 giardin, multiwavelength anomalous dispersion phasing was required to solve the alpha-14 giardin structure, indicating significant structural differences between these two members of the alpha giardin family. Unlike most annexin structures, which typically possess N-terminal domains, alpha-14 giardin is composed of only a core domain, followed by a C-terminal extension that may serve as a ligand for binding to cytoskeletal protein partners in Giardia. In the Ca(2+)-bound structure we detected five bound calcium ions, one of which is a novel, highly coordinated calcium-binding site not previously observed in annexin structures. This novel high-affinity calcium-binding site is composed of seven protein donor groups, a feature rarely observed in crystal structures. In addition, phospholipid-binding assays suggest that alpha-14 giardin exhibits calcium-dependent binding to phospholipids that coordinate cytoskeletal disassembly/assembly during differentiation of the parasite.

Reviews citing this publication (1)

  1. Parasite annexins--new molecules with potential for drug and vaccine development. Hofmann A, Osman A, Leow CY, Driguez P, McManus DP, Jones MK. Bioessays 32 967-976 (2010)

Articles citing this publication (7)

  1. Dual acylation accounts for the localization of {alpha}19-giardin in the ventral flagellum pair of Giardia lamblia. Saric M, Vahrmann A, Niebur D, Kluempers V, Hehl AB, Scholze H. Eukaryotic Cell 8 1567-1574 (2009)
  2. Alpha-1 giardin is an annexin with highly unusual calcium-regulated mechanisms. Weeratunga SK, Osman A, Hu NJ, Wang CK, Mason L, Svärd S, Hope G, Jones MK, Hofmann A. J. Mol. Biol. 423 169-181 (2012)
  3. Crystal structure and immunological properties of the first annexin from Schistosoma mansoni: insights into the structural integrity of the schistosomal tegument. Leow CY, Willis C, Osman A, Mason L, Simon A, Smith BJ, Gasser RB, Jones MK, Hofmann A. FEBS J. 281 1209-1225 (2014)
  4. Identification of α-11 giardin as a flagellar and surface component of Giardia lamblia. Kim J, Lee HY, Lee MA, Yong TS, Lee KH, Park SJ. Exp. Parasitol. 135 227-233 (2013)
  5. Comparative Cell Biology and Evolution of Annexins in Diplomonads. Einarsson E, Ástvaldsson Á, Hultenby K, Andersson JO, Svärd SG, Jerlström-Hultqvist J. mSphere 1 (2016)
  6. Differential protein expression and post-translational modifications in metronidazole-resistant Giardia duodenalis. Emery SJ, Baker L, Ansell BRE, Mirzaei M, Haynes PA, McConville MJ, Svärd SG, Jex AR. Gigascience 7 (2018)
  7. Morita-Baylis-Hillman adducts derived from thymol: synthesis, in silico studies and biological activity against Giardia lamblia. Xavier FJS, Lira AB, Verissimo GC, de S Saraiva FS, de Oliveira Filho AA, de Souza-Fagundes EM, de F F M Diniz M, Gomes MA, Castro AC, Silva FPL, Lima-Junior CG, Vasconcellos MLAA. Mol Divers (2021)


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