scholarly journals Actinobacteria challenge the paradigm: A unique protein architecture for a well-known, central metabolic complex

2021 ◽  
Vol 118 (48) ◽  
pp. e2112107118
Author(s):  
Eduardo M. Bruch ◽  
Pierre Vilela ◽  
Lu Yang ◽  
Alexandra Boyko ◽  
Norik Lexa-Sapart ◽  
...  

α-oxoacid dehydrogenase complexes are large, tripartite enzymatic machineries carrying out key reactions in central metabolism. Extremely conserved across the tree of life, they have been, so far, all considered to be structured around a high–molecular weight hollow core, consisting of up to 60 subunits of the acyltransferase component. We provide here evidence that Actinobacteria break the rule by possessing an acetyltranferase component reduced to its minimally active, trimeric unit, characterized by a unique C-terminal helix bearing an actinobacterial specific insertion that precludes larger protein oligomerization. This particular feature, together with the presence of an odhA gene coding for both the decarboxylase and the acyltransferase domains on the same polypetide, is spread over Actinobacteria and reflects the association of PDH and ODH into a single physical complex. Considering the central role of the pyruvate and 2-oxoglutarate nodes in central metabolism, our findings pave the way to both therapeutic and metabolic engineering applications.

2000 ◽  
Vol 275 (33) ◽  
pp. 25139-25145 ◽  
Author(s):  
David H. Ho ◽  
Karen Badellino ◽  
Frank A. Baglia ◽  
Mao-Fu Sun ◽  
Ming-Ming Zhao ◽  
...  

Materials ◽  
2021 ◽  
Vol 14 (5) ◽  
pp. 1077
Author(s):  
Romisuhani Ahmad ◽  
Mohd Mustafa Al Bakri Abdullah ◽  
Wan Mastura Wan Ibrahim ◽  
Kamarudin Hussin ◽  
Fakhryna Hannanee Ahmad Zaidi ◽  
...  

The primary motivation of developing ceramic materials using geopolymer method is to minimize the reliance on high sintering temperatures. The ultra-high molecular weight polyethylene (UHMWPE) was added as binder and reinforces the nepheline ceramics based geopolymer. The samples were sintered at 900 °C, 1000 °C, 1100 °C, and 1200 °C to elucidate the influence of sintering on the physical and microstructural properties. The results indicated that a maximum flexural strength of 92 MPa is attainable once the samples are used to be sintered at 1200 °C. It was also determined that the density, porosity, volumetric shrinkage, and water absorption of the samples also affected by the sintering due to the change of microstructure and crystallinity. The IR spectra reveal that the band at around 1400 cm−1 becomes weak, indicating that sodium carbonate decomposed and began to react with the silica and alumina released from gels to form nepheline phases. The sintering process influence in the development of the final microstructure thus improving the properties of the ceramic materials.


2020 ◽  
Vol 27 ◽  
pp. 2169-2173
Author(s):  
B. Suresha ◽  
B. Harshavardhan ◽  
Ashwij M. Rao ◽  
U.R. Koushik ◽  
R. Hemanth

2007 ◽  
Vol 45 (1) ◽  
pp. 73-79 ◽  
Author(s):  
Akiyoshi Sakai ◽  
Sumio Akifusa ◽  
Naoki Itano ◽  
Koji Kimata ◽  
Taro Kawamura ◽  
...  

2005 ◽  
Vol 16 (10) ◽  
pp. 4745-4754 ◽  
Author(s):  
Daniel M. Meyer ◽  
Pascal Crottet ◽  
Bohumil Maco ◽  
Elena Degtyar ◽  
Dan Cassel ◽  
...  

The mechanism of AP-1/clathrin coat formation was analyzed using purified adaptor proteins and synthetic liposomes presenting tyrosine sorting signals. AP-1 adaptors recruited in the presence of Arf1·GTP and sorting signals were found to oligomerize to high-molecular-weight complexes even in the absence of clathrin. The appendage domains of the AP-1 adaptins were not required for oligomerization. On GTP hydrolysis induced by the GTPase-activating protein ArfGAP1, the complexes were disassembled and AP-1 dissociated from the membrane. AP-1 stimulated ArfGAP1 activity, suggesting a role of AP-1 in the regulation of the Arf1 “GTPase timer.” In the presence of cytosol, AP-1 could be recruited to liposomes without sorting signals, consistent with the existence of docking factors in the cytosol. Under these conditions, however, AP-1 remained monomeric, and recruitment in the presence of GTP was short-lived. Sorting signals allowed stable recruitment and oligomerization also in the presence of cytosol. These results suggest a mechanism whereby initial assembly of AP-1 with Arf1·GTP and ArfGAP1 on the membrane stimulates Arf1 GTPase activity, whereas interaction with cargo induces oligomerization and reduces the rate of GTP hydrolysis, thus contributing to efficient cargo sorting.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 20504-20504
Author(s):  
B. Rikhof ◽  
J. van Doorn ◽  
A. Suurmeijer ◽  
M. Rautenberg ◽  
P. Jager ◽  
...  

20504 Background: Non-islet cell tumor induced hypoglycemia (NICTH) has been reported anecdotically in patients with a GIST and is associated with increased plasma levels of ‘big’-IGF-II, a high molecular weight form of IGF-II. The role of IGF-II in GIST is unknown. In non- GIST cancer, it has been suggested to be an autocrine growth factor, mainly acting by its major growth promoting receptors IGF-1 receptor (IGF- 1R) and the isoform A of the insulin receptor (IR). We investigated the clinical and biological relevance of (‘big’-)IGF-II in GIST. Methods: Plasma levels of ‘big’-IGF-II, and their relationship with disease status and NICTH, were determined in 25 consecutive GIST patients treated with imatinib (n=24) or sunitinib (n=1). Plasma samples were collected prior to, 1 week, and median 5 months after start of treatment. The levels of ‘big’-IGF-II were measured by specific radioimmunoassay (RIA). Results were compared with those obtained from healthy subjects and expressed as standard deviation scores (SDS). Paraffin-embedded GISTs (n=69) were analyzed for IGF-II, IGF-1R and IR expression by RNA in situ hybridization and immunohistochemistry (IHC). IGF-II secretion by the GIST882 cell line was analyzed by ELISA and western blotting. Results: Before treatment and/or during follow-up, 4 of 25 patients (16%) showed increased (i.e. SDS >2.0) plasma levels of ‘big’-IGF-II. Three of them developed NICTH. Patients with metastatic disease, high serum LDH, or total tumor size >12 cm had the highest ‘big’-IGF-II levels (for all p<0.05). 87% of GISTs expressed IGF-II mRNA, being excessive in tumors from patients with NICTH. These results were confirmed by IHC. GIST882 cells secreted mainly high molecular weight forms of IGF-II. The various GISTs and GIST882 cells did not express IGF-1R or IR. Conclusions: NICTH seems not to be a rare phenomenon in GIST patients. We showed for the first time that most GISTs express and secrete (‘big’-)IGF-II. Therefore, it is likely that many patients are at risk of developing NICTH, presumably especially in case of high tumor bulk. The exact role of (‘big’-)IGF-II in GIST is still not elucidated, as it does not seem to act as an autocrine growth factor since IGF-IR and IR isoform A are lacking. No significant financial relationships to disclose.


1997 ◽  
Vol 23 (2) ◽  
pp. 102-112 ◽  
Author(s):  
R. Mahesparan ◽  
B. B. Tysnes ◽  
K. Edvardsen ◽  
H. K. Haugeland ◽  
I. Garcia Cabrera ◽  
...  

1954 ◽  
Vol 32 (12) ◽  
pp. 1100-1111 ◽  
Author(s):  
J. D. McGilvery ◽  
A. E. Scott

The formation of sodium triphosphate by calcination, below the sodium triphosphate fusion point, of various phosphate mixtures of over-all composition 5Na2O.3P2O5.xH2O was investigated. Water plays an important role, decreasing the amounts of pyrophosphate and high molecular weight polyphosphate impurities and increasing the reaction rate under certain conditions. It is suggested that water catalyzes the reactions by: (1) facilitating ionic diffusion, (2) hydrolyzing —P—O—P—linkages, and (3) assisting in the crystallization of sodium triphosphate. With ortho- and pyro-phosphate mixtures temperatures of about 300 °C. and higher are necessary for the rapid formation of sodium triphosphate. With glasses of the composition 5Na2O.3P2O5 good yields may be obtained at temperatures as low as 250 °C. when water is present.


1978 ◽  
Vol 312 (1 Fibroblast Su) ◽  
pp. 299-316 ◽  
Author(s):  
Bruce R. Zetter ◽  
Gail R. Martin ◽  
Charles R. Birdwell ◽  
Denis Gospodarowicz

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