Crystal structure and immunological properties of the first annexin from Schistosoma mansoni: insights into the structural integrity of the schistosomal tegument.
نویسندگان
چکیده
Schistosomiasis is a major parasitic disease of humans, second only to malaria in its global impact. The disease is caused by digenean trematodes that infest the vasculature of their human hosts. These flukes are limited externally by a body wall composed of a syncytial epithelium, the apical surface membrane of which is a parasitism-adapted dual membrane complex. Annexins are thought to be of integral importance for the stability of this apical membrane system. Here, we present the first structural and immunobiochemical characterization of an annexin from Schistosoma mansoni. The crystal structure of annexin B22 confirms the presence of the previously predicted α-helical segment in the II/III linker and reveals a covalently linked head-to-head dimer. From the calcium-bound crystal structure of this protein, canonical type II, type III and B site positions are occupied, and a novel binding site has been identified. The dimer arrangement observed in the crystal structure suggests the presence of two prominent features, a potential non-canonical membrane binding site and a potential binding groove opposite to the former. Results from transcriptional profiling during development show that annexin B22 expression is correlated with life stages of the parasite that possess the syncytial tegument layer, and ultrastructural localization by immuno-electron microscopy confirms the occurrence of annexins in the tegument of S. mansoni. Data from membrane binding and aggregation assays indicate the presence of differential molecular mechanisms and support the hypothesis of annexin B22 providing structural integrity in the tegument.
منابع مشابه
Adhesion and co-stimulatory molecules in the pathogenesis of hepatic and intestinal schistosomiasis mansoni.
Infection of a susceptible host with the blood fluke Schistosoma mansoni results in the formation of periovular granulomas and subsequent fibrosis in the target organs. Granulomogenesis and fibrogenesis are mediated by immunological events which require cell-cell and cell-matrix interactions. In this review, the role of adhesion and co-stimulatory molecules in the genesis of the schistosomal pa...
متن کاملProlyl Oligopeptidase from the Blood Fluke Schistosoma mansoni: From Functional Analysis to Anti-schistosomal Inhibitors
BACKGROUND Blood flukes of the genus Schistosoma cause schistosomiasis, a parasitic disease that infects over 240 million people worldwide, and for which there is a need to identify new targets for chemotherapeutic interventions. Our research is focused on Schistosoma mansoni prolyl oligopeptidase (SmPOP) from the serine peptidase family S9, which has not been investigated in detail in trematod...
متن کاملAbundance of tegument surface proteins in the human blood fluke Schistosoma mansoni determined by QconCAT proteomics.
The schistosome tegument provides a major interface with the host blood stream in which it resides. Our recent proteomic studies have identified a range of proteins present in the complex tegument structure, and two models of protective immunity have implicated surface proteins as mediating antigens. We have used the QconCAT technique to evaluate the relative and absolute amounts of tegument pr...
متن کاملAntioxidant effects of gold nanoparticles on Schistosoma mansoni induced granuloma, in vitro
Objective(s): Schistosomiasis and hepatitis C virus [HCV] co-infection is common among the Egyptian population. Co-infected patients have higher rate of chronic hepatitis, cirrhosis and hepatocellular carcinoma. The aim of the present study was to investigate the potential role of gold nanoparticles on granuloma in vitro. Materials and Methods: In the current study, granulocytes were isolated f...
متن کاملMolecular and functional characterization of a Schistosoma bovis annexin: fibrinolytic and anticoagulant activity.
Annexins belong to an evolutionarily conserved multigene family of proteins expressed throughout the animal and plant kingdoms. Although they are soluble cytosolic proteins that lack signal sequences, they have also been detected in extracellular fluids and have been associated with cell surface membranes, where they could be involved in anti-haemostatic and anti-inflammatory functions. Schisto...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The FEBS journal
دوره 281 4 شماره
صفحات -
تاریخ انتشار 2014