Drivers of Hsp104 potentiation revealed by scanning mutagenesis of the middle domain

2021 ◽  
Author(s):  
Jeremy J. Ryan ◽  
Aaron Bao ◽  
Braxton Bell ◽  
Cendi Ling ◽  
Meredith E. Jackrel
Keyword(s):  
Middle Domain

scholarly journals The Middle Domain of Hsp90 Acts as a Discriminator between Different Types of Client Proteins

2006 ◽  
Vol 26 (22) ◽  
pp. 8385-8395 ◽  
Author(s):  
Patricija Hawle ◽  
Martin Siepmann ◽  
Anja Harst ◽  
Marco Siderius ◽  
H. Peter Reusch ◽  
...  
Keyword(s):  
Atp Hydrolysis ◽  
Mutational Analysis ◽  
Fold Increase ◽  
Cellular Protein ◽  
Hydrolysis Rate ◽  
Cellular Activity ◽  
Protein Levels ◽  
Middle Domain ◽  
Client Proteins

ABSTRACT The mechanism of client protein activation by Hsp90 is enigmatic, and it is uncertain whether Hsp90 employs a common route for all proteins. Using a mutational analysis approach, we investigated the activation of two types of client proteins, glucocorticoid receptor (GR) and the kinase v-Src by the middle domain of Hsp90 (Hsp90M) in vivo. Remarkably, the overall cellular activity of v-Src was highly elevated in a W300A mutant yeast strain due to a 10-fold increase in cellular protein levels of the kinase. In contrast, the cellular activity of GR remained almost unaffected by the W300A mutation but was dramatically sensitive to S485Y and T525I exchanges. In addition, we show that mutations S485Y and T525I in Hsp90M reduce the ATP hydrolysis rate, suggesting that Hsp90 ATPase is more tightly regulated than assumed previously. Therefore, the activation of GR and v-Src has various demands on Hsp90 biochemistry and is dependent on separate functional regions of Hsp90M. Thus, Hsp90M seems to discriminate between different substrate types and to adjust the molecular chaperone for proper substrate activation.

scholarly journals Organization of the Flagellar Switch Complex ofBacillus subtilis

2018 ◽  
Vol 201 (8) ◽  
Author(s):  
Elizabeth Ward ◽  
Eun A Kim ◽  
Joseph Panushka ◽  
Tayson Botelho ◽  
Trevor Meyer ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Protein Interaction ◽  
Protein Complex ◽  
Cross Linking ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
E Coli ◽  
Middle Domain ◽  
Flagellar Rotation

ABSTRACTWhile the protein complex responsible for controlling the direction (clockwise [CW] or counterclockwise [CCW]) of flagellar rotation has been fairly well studied inEscherichia coliandSalmonella, less is known about the switch complex inBacillus subtilisor other Gram-positive species. Two component proteins (FliG and FliM) are shared betweenE. coliandB. subtilis, but in place of the protein FliN found inE. coli, theB. subtiliscomplex contains the larger protein FliY. Notably, inB. subtilisthe signaling protein CheY-phosphate induces a switch from CW to CCW rotation, opposite to its action inE. coli. Here, we have examined the architecture and function of the switch complex inB. subtilisusing targeted cross-linking, bacterial two-hybrid protein interaction experiments, and characterization of mutant phenotypes. In major respects, theB. subtilisswitch complex appears to be organized similarly to that inE. coli. The complex is organized around a ring built from the large middle domain of FliM; this ring supports an array of FliG subunits organized in a similar way to that ofE. coli, with the FliG C-terminal domain functioning in the generation of torque via conserved charged residues. Key differences fromE. coliinvolve the middle domain of FliY, which forms an additional, more outboard array, and the C-terminal domains of FliM and FliY, which are organized into both FliY homodimers and FliM heterodimers. Together, the results suggest that the CW and CCW conformational states are similar in the Gram-negative and Gram-positive switches but that CheY-phosphate drives oppositely directed movements in the two cases.IMPORTANCEFlagellar motility plays key roles in the survival of many bacteria and in the harmful action of many pathogens. Bacterial flagella rotate; the direction of flagellar rotation is controlled by a multisubunit protein complex termed the switch complex. This complex has been extensively studied in Gram-negative model species, but little is known about the complex inBacillus subtilisor other Gram-positive species. Notably, the switch complex in Gram-positive species responds to its effector CheY-phosphate (CheY-P) by switching to CCW rotation, whereas inE. coliorSalmonellaCheY-P acts in the opposite way, promoting CW rotation. In the work here, the architecture of theB. subtilisswitch complex has been probed using cross-linking, protein interaction measurements, and mutational approaches. The results cast light on the organization of the complex and provide a framework for understanding the mechanism of flagellar direction control inB. subtilisand other Gram-positive species.

scholarly journals An Acetylation Site in the Middle Domain of Hsp90 Regulates Chaperone Function

2007 ◽  
Vol 25 (1) ◽  
pp. 151-159 ◽  
Author(s):  
Bradley T. Scroggins ◽  
Kenneth Robzyk ◽  
Dongxia Wang ◽  
Monica G. Marcu ◽  
Shinji Tsutsumi ◽  
...  
Keyword(s):  
Chaperone Function ◽  
Acetylation Site ◽  
Middle Domain

5018 An anti-glaucoma agent, H-1129, binds to middle domain of Hsp90

SciVee ◽  
2012 ◽  
Author(s):  
Yoko Yoshida
Keyword(s):  
Middle Domain

Interface of the interaction of the middle domain of human translation termination factor eRF1 with eukaryotic ribosomes

2008 ◽  
Vol 42 (6) ◽  
pp. 939-948 ◽  
Author(s):  
E. V. Ivanova ◽  
E. Z. Alkalaeva ◽  
B. Birdsall ◽  
P. M. Kolosov ◽  
V. I. Polshakov ◽  
...  
Keyword(s):  
Translation Termination ◽  
Termination Factor ◽  
Middle Domain ◽  
Translation Termination Factor

Functional and physical interactions within the middle domain of the yeast mediator

2006 ◽  
Vol 276 (2) ◽  
pp. 197-210 ◽  
Author(s):  
Magnus Hallberg ◽  
Guo-Zhen Hu ◽  
Susanna Tronnersjö ◽  
Zaki Shaikhibrahim ◽  
Darius Balciunas ◽  
...  
Keyword(s):  
Middle Domain ◽  
Physical Interactions

scholarly journals Allosteric Regulation of Hsp90α’s Activity by Small Molecules Targeting the Middle Domain of the Chaperone

iScience ◽  
2020 ◽  
Vol 23 (2) ◽  
pp. 100857 ◽  
Author(s):  
Chen Zhou ◽  
Chi Zhang ◽  
Hongwen Zhu ◽  
Zhijun Liu ◽  
Haixia Su ◽  
...  
Keyword(s):  
Small Molecules ◽  
Allosteric Regulation ◽  
Middle Domain

Exploring spontaneous-event marking though parallel corpora

2015 ◽  
Vol 15 (2) ◽  
pp. 230-250
Author(s):  
Lene Nordrum
Keyword(s):  
Point Of View ◽  
Parallel Corpora ◽  
Development Path ◽  
Middle Domain ◽  
Reflexive Verbs

English ergative verbs in one-participant constructions such as ‘the door opens’ often correspond to reflexive verbs or -S forms in Norwegian and Swedish. Following Kemmer (1993), such constructions profile spontaneous-event meaning and belong to the middle domain. This study uses corpus methodology to explore spontaneous-event marking in Norwegian and Swedish from the point of view of Kemmer’s suggested two-cycle development path for middle marking in the Scandinavian languages. The results suggest that there are differences in the middle systems in the Scandinavian languages to the effect that Norwegian has completed Kemmer’s two cycles, whereas Swedish has not. Further, there is tentative indication that ergative verbs are on the increase in both Norwegian and Swedish for certain Subjects and in discipline-specific contexts, possibly due to influence from English.

Light and heavy reflexive marking

2007 ◽  
Vol 5 ◽  
pp. 239-269 ◽  
Author(s):  
Andreea S. Calude
Keyword(s):  
Current Paper ◽  
Common Denominator ◽  
Semantic Property ◽  
Human Language ◽  
Middle Domain ◽  
Cognitive Theories ◽  
The Common ◽  
Situation Types ◽  
Middle Constructions ◽  
Insight Into

In Romanian, the middle marker se is employed to encode five distinct situation types: reflexive, reciprocal, (medio-)passive, inchoative and impersonal. This work identifies the relationships among the different uses of the marker and puts forward explanations for them within a cognitive, functional framework. Following studies such as those by Faltz (1985), Haiman (1983), Haspelmath (2005), Kemmer (1993ab), Lakoff (1977), Manoliu-Manea (1994, 2000), Maldonado (1992, 1999), Manney (2000), and Yoshimura and Taylor (2004), the current paper gives a synchronic account of the Romanian Middle Domain, its organization and the relationships between the various middle constructions found inside it. Findings suggest that the semantic property of low elaboration of events (introduced by Kemmer, 1993ab) constitutes the common denominator among the different uses explored. This work provides an insight into Romanian itself, as well as a contribution to cognitive theories of human language and responds to the call for more data and further investigations of middles cross-linguistically (see Smith, 2004).

scholarly journals Structure of the Spt16 Middle Domain Reveals Functional Features of the Histone Chaperone FACT

2013 ◽  
Vol 288 (15) ◽  
pp. 10188-10194 ◽  
Author(s):  
David J. Kemble ◽  
Frank G. Whitby ◽  
Howard Robinson ◽  
Laura L. McCullough ◽  
Tim Formosa ◽  
...  
Keyword(s):  
Histone Chaperone ◽  
Middle Domain ◽  
Functional Features
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