Role of hybrid tetramer formation in gelation of haemoglobin S

Nature ◽  
1975 ◽  
Vol 256 (5519) ◽  
pp. 667-668 ◽  
Author(s):  
ROBERT M. BOOKCHIN ◽  
RONALD L. NAGEL ◽  
TANIA BALAZS
Keyword(s):  
Tetramer Formation ◽  
Haemoglobin S

scholarly journals The Carboxyl-Terminal Domain of TraR, a Streptomyces HutC Family Repressor, Functions in Oligomerization

2008 ◽  
Vol 190 (21) ◽  
pp. 7164-7169 ◽  
Author(s):  
Masakazu Kataoka ◽  
Takeshi Tanaka ◽  
Toshiyuki Kohno ◽  
Yusuke Kajiyama
Keyword(s):  
Limited Proteolysis ◽  
Sequence Information ◽  
Structural Domains ◽  
Terminal Domain ◽  
Tetramer Formation ◽  
Regulated Expression ◽  
Carboxyl Terminal ◽  
Two Hybrid

ABSTRACT Efficient conjugative transfer of the Streptomyces plasmid pSN22 is accomplished by regulated expression of the tra operon genes, traA, traB, and spdB. The TraR protein is the central transcriptional repressor regulating the expression of the tra operon and itself and is classified as a member of the HutC subfamily in the helix-turn-helix (HTH) GntR protein family. Sequence information predicts that the N-terminal domain (NTD) of TraR, containing an HTH motif, functions in binding of DNA to the cis element; however, the function of the C-terminal region remains obscure, like that for many other GntR family proteins. Here we demonstrate the domain structure of the TraR protein and explain the role of the C-terminal domain (CTD). The TraR protein can be divided into two structural domains, the NTD of M1 to R95 and the CTD of Y96 to E246, revealed by limited proteolysis. Domain expression experiments revealed that both domains retained their function. An in vitro pull-down assay using recombinant TraR proteins revealed that TraR oligomerization depended on the CTD. A bacterial two-hybrid system interaction assay revealed that the minimum region necessary for this binding is R95 to P151. A mutant TraR protein in which Leu121 was replaced by His exhibited a loss of both oligomerization ability and repressor function. An in vitro cross-linking assay revealed preferential tetramer formation by TraR and the minimum CTD. These results indicate that the C-terminal R95-to-P151 region of TraR functions to form an oligomer, preferentially a tetramer, that is essential for the repressor function of TraR.

scholarly journals A Cyclin-Binding Motif in Human SAMHD1 Is Required for Its HIV-1 Restriction, dNTPase Activity, Tetramer Formation, and Efficient Phosphorylation

2018 ◽  
Vol 92 (6) ◽  
Author(s):  
Corine St. Gelais ◽  
Sun Hee Kim ◽  
Victoria V. Maksimova ◽  
Olga Buzovetsky ◽  
Kirsten M. Knecht ◽  
...  
Keyword(s):  
Restriction Factor ◽  
Binding Motif ◽  
Functional Domain ◽  
Tetramer Formation ◽  
Intracellular Dntp ◽  
Cyclin A2 ◽  
Functional Analyses ◽  
Hiv 1 ◽  
In Cells

ABSTRACT Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) regulates intracellular deoxynucleoside triphosphate (dNTP) levels and functions as a retroviral restriction factor through its dNTP triphosphohydrolase (dNTPase) activity. Human SAMHD1 interacts with cell cycle regulatory proteins cyclin A2, cyclin-dependent kinase 1 (CDK1), and CDK2. This interaction mediates phosphorylation of SAMHD1 at threonine 592 (T592), which negatively regulates HIV-1 restriction. We previously reported that the interaction is mediated, at least in part, through a cyclin-binding motif (RXL, amino acids [aa] 451 to 453). To understand the role of the RXL motif in regulating SAMHD1 activity, we performed structural and functional analyses of RXL mutants and the effect on HIV-1 restriction. We found that the RXL mutation (R451A and L453A, termed RL/AA) disrupted SAMHD1 tetramer formation and abolished its dNTPase activity in vitro and in cells. Compared to wild-type (WT) SAMHD1, the RL/AA mutant failed to restrict HIV-1 infection and had reduced binding to cyclin A2. WT SAMHD1 and RL/AA mutant proteins were degraded by Vpx from HIV-2 but were not spontaneously ubiquitinated in the absence of Vpx. Analysis of proteasomal and autophagy degradation revealed that WT and RL/AA SAMHD1 protein levels were enhanced only when both pathways of degradation were simultaneously inhibited. Our results demonstrate that the RXL motif of human SAMHD1 is required for its HIV-1 restriction, tetramer formation, dNTPase activity, and efficient phosphorylation at T592. These findings identify a new functional domain of SAMHD1 important for its structural integrity, enzyme activity, phosphorylation, and HIV-1 restriction. IMPORTANCE SAMHD1 is the first mammalian dNTPase identified as a restriction factor that inhibits HIV-1 replication by decreasing the intracellular dNTP pool in nondividing cells, although the critical mechanisms regulating SAMHD1 function remain unclear. We previously reported that mutations of a cyclin-binding RXL motif in human SAMHD1 significantly affect protein expression levels, half-life, nuclear localization, and phosphorylation, suggesting an important role of this motif in modulating SAMHD1 functions in cells. To further understand the significance and mechanisms of the RXL motif in regulating SAMHD1 activity, we performed structural and functional analyses of the RXL motif mutation and its effect on HIV-1 restriction. Our results indicate that the RXL motif is critical for tetramer formation, dNTPase activity, and HIV-1 restriction. These findings help us understand SAMHD1 interactions with other host proteins and the mechanisms regulating SAMHD1 structure and functions in cells.

Essential Role of Proline Isomerization in Stefin B Tetramer Formation

2007 ◽  
Vol 366 (5) ◽  
pp. 1569-1579 ◽  
Author(s):  
Saša Jenko Kokalj ◽  
Gregor Gunčar ◽  
Igor Štern ◽  
Gareth Morgan ◽  
Sabina Rabzelj ◽  
...  
Keyword(s):  
Essential Role ◽  
Proline Isomerization ◽  
Tetramer Formation

Role of dactinomycin in the improved survival of children with Wilms' tumor

JAMA ◽  
1966 ◽  
Vol 195 (12) ◽  
pp. 1005-1009 ◽  
Author(s):  
D. J. Fernbach
Keyword(s):  
Wilms Tumor

Role of the allergist in diagnosis and management of patients with uveitis

JAMA ◽  
1966 ◽  
Vol 195 (3) ◽  
pp. 167-172 ◽  
Author(s):  
T. E. Van Metre
Keyword(s):  
Diagnosis And Management

The power of norms to sway fused group members

2018 ◽  
Vol 41 ◽  
Author(s):  
Winnifred R. Louis ◽  
Craig McGarty ◽  
Emma F. Thomas ◽  
Catherine E. Amiot ◽  
Fathali M. Moghaddam
Keyword(s):  
Evolutionary Anthropology ◽  
Normative Systems ◽  
Violent Extremism ◽  
Identity Fusion ◽  
Group Members

AbstractWhitehouse adapts insights from evolutionary anthropology to interpret extreme self-sacrifice through the concept of identity fusion. The model neglects the role of normative systems in shaping behaviors, especially in relation to violent extremism. In peaceful groups, increasing fusion will actually decrease extremism. Groups collectively appraise threats and opportunities, actively debate action options, and rarely choose violence toward self or others.

Elaborating the role of reflection and individual differences in the study of folk-economic beliefs

2018 ◽  
Vol 41 ◽  
Author(s):  
Kevin Arceneaux
Keyword(s):  
Decision Making ◽  
Individual Differences ◽  
Cognitive Processes ◽  
Evolutionary History ◽  
Behavioral Responses ◽  
History Of ◽  
Economic Beliefs

AbstractIntuitions guide decision-making, and looking to the evolutionary history of humans illuminates why some behavioral responses are more intuitive than others. Yet a place remains for cognitive processes to second-guess intuitive responses – that is, to be reflective – and individual differences abound in automatic, intuitive processing as well.

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