Document Detail


Characterization of Anopheles gambiae transglutaminase 3 (AgTG3) and its native substrate Plugin.
MedLine Citation:
PMID:  23288850     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Binh V Le; Jennifer B Nguyen; Shankar Logarajah; Bo Wang; Jacob Marcus; Hazel P Williams; Flaminia Catteruccia; Richard H G Baxter
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-03
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  288     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-18     Completed Date:  2013-04-29     Revised Date:  2014-05-02    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4844-53     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Anopheles gambiae / enzymology*
Calcium / chemistry
Cross-Linking Reagents / chemistry
Cytoplasm / metabolism
Dimerization
Female
Male
Mass Spectrometry / methods
Models, Chemical
Molecular Sequence Data
Peptides / chemistry
Protein Binding
Protein Structure, Tertiary
Sequence Homology, Amino Acid
Structure-Activity Relationship
Transglutaminases / chemistry*,  metabolism
Grant Support
ID/Acronym/Agency:
K22AI085112-0/AI/NIAID NIH HHS; T32 GM008283/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Cross-Linking Reagents; 0/Peptides; EC 2.3.2.13/Transglutaminases; SY7Q814VUP/Calcium
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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