scholarly journals Inverse control of Rab proteins by Yersinia ADP-ribosyltransferase and glycosyltransferase related to clostridial glucosylating toxins

2020 ◽  
Vol 6 (11) ◽  
pp. eaaz2094
Author(s):  
G. Stefan Ost ◽  
Christophe Wirth ◽  
Xenia Bogdanović ◽  
Wei-Chun Kao ◽  
Björn Schorch ◽  
...  
Keyword(s):  
Potassium Ion ◽  
Rab Proteins ◽  
Gtp Hydrolysis ◽  
Inverse Control ◽  
Amino Terminal ◽  
Translocation Domain ◽  
Carboxyl Terminal ◽  
Function Relationship ◽  
Relationship Of ◽  
Adp Ribosyltransferase

We identified a glucosyltransferase (YGT) and an ADP-ribosyltransferase (YART) in Yersinia mollaretii, highly related to glucosylating toxins from Clostridium difficile, the cause of antibiotics-associated enterocolitis. Both Yersinia toxins consist of an amino-terminal enzyme domain, an autoprotease domain activated by inositol hexakisphosphate, and a carboxyl-terminal translocation domain. YGT N-acetylglucosaminylates Rab5 and Rab31 at Thr52 and Thr36, respectively, thereby inactivating the Rab proteins. YART ADP-ribosylates Rab5 and Rab31 at Gln79 and Gln64, respectively. This activates Rab proteins by inhibiting GTP hydrolysis. We determined the crystal structure of the glycosyltransferase domain of YGT (YGTG) in the presence and absence of UDP at 1.9- and 3.4-Å resolution, respectively. Thereby, we identified a previously unknown potassium ion–binding site, which explains potassium ion–dependent enhanced glycosyltransferase activity in clostridial and related toxins. Our findings exhibit a novel type of inverse regulation of Rab proteins by toxins and provide new insights into the structure-function relationship of glycosyltransferase toxins.

STUDIES ON THE MECHANISM OF SOMATOSTATIN ACTION ON INSULIN RELEASE

1977 ◽  
Vol 85 (3) ◽  
pp. 579-586 ◽  
Author(s):  
S. Efendić ◽  
P. E. Lins ◽  
R. Luft ◽  
H. Sievertsson ◽  
G. Westin-Sjödal
Keyword(s):  
Amino Acids ◽  
Insulin Release ◽  
Cyclic Peptide ◽  
The Other ◽  
Perfused Rat Pancreas ◽  
Rat Pancreas ◽  
Amino Terminal ◽  
Structure Activity ◽  
Carboxyl Terminal ◽  
Relationship Of

ABSTRACT Eighteen analogues of somatostatin have been used in order to elucidate the structure-activity relationship of the peptide on the release of insulin and glucagon from the isolated perfused rat pancreas. Neither the amino terminal nor a free carboxyl terminal seemed to be essential for the activity of the cyclic peptide. Addition of amino acids to the amino terminal did not decrease the activity. On the other hand, minor changes in the structure of linear somatostatin, which lead to the loss of ability to form a cyclic peptide, impaired the activity. Deletion of Asn5 was accompanied by decreased action on glucagon but not on insulin release. It seems that the major actions of somatostatin on the pancreas are bound to the amino acid sequence 4–13 in the molecule and to the ability of the molecule to cyclize.

High- And Low-Affinity Heparin Binding Proteins From Bovine Platelets

1981 ◽  
Author(s):  
Raymond E Ciaglowski ◽  
Daniel A Walz
Keyword(s):  
Platelet Factor 4 ◽  
Heparin Binding ◽  
Cellulose Acetate Electrophoresis ◽  
Platelet Factor ◽  
Amino Terminal ◽  
Binding Domains ◽  
Specific Proteins ◽  
Related Variant ◽  
Function Relationship ◽  
Relationship Of

The class of platelet-specific proteins which displays anti heparin and/or growth stimulating activities includes: high affinity platelet factor 4 (HA-PF-4), low affinity platelet factor 4 (LA-PF-4) and its closely related variant β-thromboglobulin (β-TG), and platelet derived growth factors) (PDGF). In an effort to determine to what extent these proteins and their activities might be broad-based, a comparative study using bovine platelets has been undertaken. Fresh, washed bovine platelets were either thrombin stimulated or freeze-fractured and the ensuing supernatants chromatographed on either heparin-Sepharose (HS) or dextran- sulfate-Sepharose (DSS). Bovine protein which eluted with either 1.0M NaCl (HS) or 1.5M NaCl (DSS) was subsequently gel filtered to homogeneity. Using S2222 chromogenic assays, the bovine protein (9000 dal tons) and human HA-PF-4 (7800 dal tons) each had similar heparin neutral ization equivalence, about 40 U/mg. Using 3T3 cells, growth promoting activity was not found to be associated with the purified bovine HA- PF-4. Although bovine HA-PF-4 has 15 additional residues from the amino terminal end of human HA-PF-4, the acidic, neutral and basic regions have remained similar. HSand DSS fractions from thrombin released platelets eluted with 0.5M NaCl and gel filtered yielded a homogeneous protein of molecular weight 12,000 dal tons. This product has a heparin neutralization activity of approximately 2 U/mg; cellulose acetate electrophoresis of the bovine protein migrated into the gammaglobulin region, and we have consequently referred to it as bovine LA-PF-4. The bovine LA-PF-4 protein had 3T3 growth stimulating activity at least comparable to that of a DSS intermediate salt eluted fraction. The amino terminal 12 residues of bovine LA-PF-4 are not similar to human LA-PF-4 or β-TG. We conclude that these bovine anti heparin proteins are functionally homologous to their human counterparts. We are currently completing the sequence of bovine HA-PF-4 in order to establish the structure-function relationship of the heparin binding domains of these proteins.

scholarly journals Evolution of the hedgehog Gene Family

Genetics ◽  
1996 ◽  
Vol 142 (3) ◽  
pp. 965-972 ◽  
Author(s):  
Sudhir Kumar ◽  
Kristi A Balczarek ◽  
Zhi-Chun Lai
Keyword(s):  
Intercellular Communication ◽  
Short Range ◽  
Gene Duplications ◽  
Future Directions ◽  
Amino Terminal ◽  
Terminal Fragment ◽  
Carboxyl Terminal ◽  
Multicellular Organisms ◽  
Amino Terminal Fragment

Abstract Effective intercellular communication is an important feature in the development of multicellular organisms. Secreted hedgehog (hh) protein is essential for both long- and short-range cellular signaling required for body pattern formation in animals. In a molecular evolutionary study, we find that the vertebrate homologs of the Drosophila hh gene arose by two gene duplications: the first gave rise to Desert hh, whereas the second produced the Indian and Sonic hh genes. Both duplications occurred before the emergence of vertebrates and probably before the evolution of chordates. The amino-terminal fragment of the hh precursor, crucial in long- and short-range intercellular communication, evolves two to four times slower than the carboxyl-terminal fragment in both Drosophila hh and its vertebrate homologues, suggesting conservation of mechanism of hh action in animals. A majority of amino acid substitutions in the amino- and carboxyl-terminal fragments are conservative, but the carboxyl-terminal domain has undergone extensive insertion-deletion events while maintaining its autocleavage protease activity. Our results point to similarity of evolutionary constraints among sites of Drosophila and vertebrate hh homologs and suggest some future directions for understanding the role of hh genes in the evolution of developmental complexity in animals.

Structure–property–function relationship of fluorescent conjugated microporous polymers

2021 ◽  
Author(s):  
M. G. Monika Bai ◽  
H. Vignesh Babu ◽  
V. Lakshmi ◽  
M. Rajeswara Rao
Keyword(s):  
Long Range ◽  
Structure Property ◽  
Porous Organic Polymers ◽  
Aggregation Induced Emission ◽  
Microporous Polymers ◽  
Exciton Migration ◽  
Wide Range ◽  
Function Relationship ◽  
Relationship Of ◽  
Conjugated Microporous Polymers

Fluorescent porous organic polymers are a unique class of materials owing to their strong aggregation induced emission, long range exciton migration and permanent porosity, thus envisioned to possess a wide range of applications (sensing, OLEDs).

Morphology-Function Relationship of Thermoelectric Nanocomposite Films from PEDOT:PSS with Silicon Nanoparticles

2017 ◽  
Vol 3 (8) ◽  
pp. 1700181 ◽  
Author(s):  
Nitin Saxena ◽  
Mihael Čorić ◽  
Anton Greppmair ◽  
Jan Wernecke ◽  
Mika Pflüger ◽  
...  
Keyword(s):  
Silicon Nanoparticles ◽  
Nanocomposite Films ◽  
Function Relationship ◽  
Relationship Of

scholarly journals High-resolution single-cell 3D-models of chromatin ensembles during Drosophila embryogenesis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qiu Sun ◽  
Alan Perez-Rathke ◽  
Daniel M. Czajkowsky ◽  
Zhifeng Shao ◽  
Jie Liang
Keyword(s):  
High Resolution ◽  
Single Cell ◽  
3D Models ◽  
Computational Method ◽  
Midblastula Transition ◽  
Genome Wide ◽  
Large Ensembles ◽  
Chromatin Folding ◽  
Function Relationship ◽  
Relationship Of

AbstractSingle-cell chromatin studies provide insights into how chromatin structure relates to functions of individual cells. However, balancing high-resolution and genome wide-coverage remains challenging. We describe a computational method for the reconstruction of large 3D-ensembles of single-cell (sc) chromatin conformations from population Hi-C that we apply to study embryogenesis in Drosophila. With minimal assumptions of physical properties and without adjustable parameters, our method generates large ensembles of chromatin conformations via deep-sampling. Our method identifies specific interactions, which constitute 5–6% of Hi-C frequencies, but surprisingly are sufficient to drive chromatin folding, giving rise to the observed Hi-C patterns. Modeled sc-chromatins quantify chromatin heterogeneity, revealing significant changes during embryogenesis. Furthermore, >50% of modeled sc-chromatin maintain topologically associating domains (TADs) in early embryos, when no population TADs are perceptible. Domain boundaries become fixated during development, with strong preference at binding-sites of insulator-complexes upon the midblastula transition. Overall, high-resolution 3D-ensembles of sc-chromatin conformations enable further in-depth interpretation of population Hi-C, improving understanding of the structure-function relationship of genome organization.

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