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J Biol Chem. 2013 Feb 15;288(7):4844-53. doi: 10.1074/jbc.M112.435347. Epub 2013 Jan 3.

Characterization of Anopheles gambiae transglutaminase 3 (AgTG3) and its native substrate Plugin.

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  • 1Department of Chemistry, Yale University, New Haven, Connecticut 06520-81070, USA.

Abstract

Male Anopheles mosquitoes coagulate their seminal fluids via cross-linking of a substrate, called Plugin, by the seminal transglutaminase AgTG3. Formation of the "mating plug" by cross-linking Plugin is necessary for efficient sperm storage by females. AgTG3 has a similar degree of sequence identity (~30%) to both human Factor XIII (FXIII) and tissue transglutaminase 2 (hTG2). Here we report the solution structure and in vitro activity for the cross-linking reaction of AgTG3 and Plugin. AgTG3 is a dimer in solution and exhibits Ca(2+)-dependent nonproteolytic activation analogous to cytoplasmic FXIII. The C-terminal domain of Plugin is predominantly α-helical with extended tertiary structure and oligomerizes in solution. The specific activity of AgTG3 was measured as 4.25 × 10(-2) units mg(-1). AgTG3 is less active than hTG2 assayed using the general substrate TVQQEL but has 8-10× higher relative activity when Plugin is the substrate. Mass spectrometric analysis of cross-linked Plugin detects specific peptides including a predicted consensus motif for cross-linking by AgTG3. These results support the development of AgTG3 inhibitors as specific and effective chemosterilants for A. gambiae.

PMID:
23288850
[PubMed - indexed for MEDLINE]
PMCID:
PMC3576089
Free PMC Article
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