Apo and calcium-bound crystal structures of Alpha-11 giardin, an unusual annexin from Giardia lamblia.

Apo and calcium-bound crystal structures of Alpha-11 giardin, an unusual annexin from Giardia lamblia. Research Abstract Details 

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Apo and calcium-bound crystal structures of Alpha-11 giardin, an unusual annexin from Giardia lamblia. Abstract Text:

Puja Pathuri,Emily Tam Nguyen,Staffan G ,Hartmut Luecke,

Alpha-11 giardin is a member of the multi-gene alpha-giardin family in the intestinal protozoan, Giardia lamblia. This gene family shares an ancestry with the annexin super family, whose common characteristic is calcium-dependent binding to membranes that contain acidic phospholipids. Several alpha giardins are highly expressed during parasite-induced diarrhea in humans. Despite being a member of a large family of proteins, little is known about the function and cellular localization of alpha-11 giardin, although giardins are often associated with the cytoskeleton. It has been shown that Giardia exhibits high levels of alpha-11 giardin mRNA transcript throughout its life cycle; however, constitutive over-expression of this protein is lethal to the parasite. Determining the three-dimensional structure of an alpha-giardin is essential to identifying functional domains shared in the alpha-giardin family. Here we report the crystal structures of the apo and Ca(2+)-bound forms of alpha-11 giardin, the first alpha giardin to be characterized structurally. Crystals of apo and Ca(2+)-bound alpha-11 giardin diffracted to 1.1 A and 2.93 A, respectively. The crystal structure of selenium-substituted apo alpha-11 giardin reveals a planar array of four tandem repeats of predominantly alpha-helical domains, reminiscent of previously determined annexin structures, making this the highest-resolution structure of an annexin to date. The apo alpha-11 giardin structure also reveals a hydrophobic core formed between repeats I/IV and II/III, a region typically hydrophilic in other annexins. Surprisingly, the Ca(2+)-bound structure contains only a single calcium ion, located in the DE loop of repeat I and coordinated differently from the two types of calcium sites observed in previous annexin structures. The apo and Ca(2+)-bound alpha-11 giardin structures assume overall similar conformations; however, Ca(2+)-bound alpha-11 giardin crystallized in a lower-symmetry space group with four molecules in the asymmetric unit. Vesicle-binding studies suggest that alpha-11 giardin, unlike most other annexins, does not bind to vesicles composed of acidic phospholipids in a calcium-dependent manner.

Apo and calcium-bound crystal structures of Alpha-11 giardin, an unusual annexin from Giardia lamblia. Publishing Authors By Initials

P Pathuri,ET Nguyen,SG ,H Luecke,

For similar investigative techniques: genetic techniques: sequence alignment research abstracts see: investigative techniques: genetic techniques: sequence alignment research

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Apo and calcium-bound crystal structures of Alpha-11 giardin, an unusual annexin from Giardia lamblia. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of molecular biology

VOLUME: 368

Page Numbers: 493-508

Journal Abbreviation: J. Mol. Biol.

ISSN: 0022-2836

DAY: 20

MONTH: 02

YEAR: 2007

Apo and calcium-bound crystal structures of Alpha-11 giardin, an unusual annexin from Giardia lamblia. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985088

Apo and calcium-bound crystal structures of Alpha-11 giardin, an unusual annexin from Giardia lamblia. Keywords Mesh Terms:

KEYWORDS: Sequence Alignment

MESH TERMS: chemistry

Chemical & Substance for Abstract: Apo and calcium-bound crystal structures of Alpha-11 giardin, an unusual annexin from Giardia lamblia. Information

Substance Name: Calcium

Registry Number: 7440-70-2

Grant and Affiliation Information for Apo and calcium-bound crystal structures of Alpha-11 giardin, an unusual annexin from Giardia lamblia.

AFFILIATION: Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.

Country: England

AGENCY: United States NIGMS

GRANT: R01-GM067808

ACRONYM: GM

MEDLINETA: J Mol Biol

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