UCSD Phar201 Structural Aspects of Protein Protein Interactions

SciVee ◽  
2011 ◽  
Author(s):  
Philip Bourne
Keyword(s):  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Structural Aspects

scholarly journals The 14-3-3 Proteins as Important Allosteric Regulators of Protein Kinases

2020 ◽  
Vol 21 (22) ◽  
pp. 8824
Author(s):  
Veronika Obsilova ◽  
Tomas Obsil
Keyword(s):  
Protein Interactions ◽  
Cell Cycle Progression ◽  
State Of The Art ◽  
Review Article ◽  
Protein Protein Interactions ◽  
Cycle Progression ◽  
Kinase Regulation ◽  
Functional Consequences ◽  
Allosteric Regulators ◽  
Structural Aspects

Phosphorylation by kinases governs many key cellular and extracellular processes, such as transcription, cell cycle progression, differentiation, secretion and apoptosis. Unsurprisingly, tight and precise kinase regulation is a prerequisite for normal cell functioning, whereas kinase dysregulation often leads to disease. Moreover, the functions of many kinases are regulated through protein–protein interactions, which in turn are mediated by phosphorylated motifs and often involve associations with the scaffolding and chaperon protein 14-3-3. Therefore, the aim of this review article is to provide an overview of the state of the art on 14-3-3-mediated kinase regulation, focusing on the most recent mechanistic insights into these important protein–protein interactions and discussing in detail both their structural aspects and functional consequences.

Cytochrome P-450 and NADPH-Cytochrome c (P-450) Reductase in Reconstituted Phospholipid Vesicles as Demonstrated by Negative Staining Techniques

1981 ◽  
Vol 39 ◽  
pp. 558-559
Author(s):  
Jane H. Dees ◽  
Linda K. Parkhill ◽  
L. Dean Coe ◽  
Betty Ann Germany ◽  
R. T. Okita ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Protein Interactions ◽  
Membrane Vesicles ◽  
Protein Protein Interactions ◽  
Ultrastructural Studies ◽  
Nadph Cytochrome ◽  
Hydrophobic Tail ◽  
Staining Techniques ◽  
Cytochrome P 450 ◽  
Structural Aspects

Artificial membrane vesicles or liposomes have become an accepted model for the study of enzyme-membrane interactions under controlled conditions.The development of reconstituted vesicle models for the microsomal mixed function oxidase enzymes has provided a system in which to study not only the biochemistry of these enzymes in a near physiologic milieu, but also structural aspects of the protein-phospholipid and protein-protein interactions. Ultrastructural studies on liposomes reconstituted with NADPH- cytochrome c (P-450) reductase (an amphipathic protein, 78,000 daltons, thought to be partially embedded in the microsomal membrane by its hydrophobic tail), and cytochrome P-450 (a hydrophobic protein, about 50,000 daltons, thought to be embedded within the lipid bilayer) either singly or together, should reveal information on whether these proteins are randomly arranged in the membrane or arranged in an ordered manner, an issue currently debated among cytochrome P-450 researchers.

The human androgen receptor AF1 transactivation domain: interactions with transcription factor IIF and molten-globule-like structural characteristics

2006 ◽  
Vol 34 (6) ◽  
pp. 1054-1057 ◽  
Author(s):  
D.N. Lavery ◽  
I.J. McEwan
Keyword(s):  
Transcription Factor ◽  
Androgen Receptor ◽  
Protein Interactions ◽  
Structural Characteristics ◽  
Molten Globule ◽  
Transactivation Domain ◽  
Protein Protein Interactions ◽  
Induced Folding ◽  
Transcription Factor Iif ◽  
Structural Aspects

The AR (androgen receptor) is a ligand-activated transcription factor and member of the steroid receptor superfamily. The AR responds to the ligands testosterone and dihydrotestosterone and activates multiple downstream genes required in development and reproduction. During the events of transactivation, the AR makes specific protein–protein interactions with several basal transcription factors such as TBP (TATA-box-binding protein) and TFIIF (transcription factor IIF). These interactions occur predominantly within a defined region termed AF1 (activation function-1) located within the highly disordered N-terminal domain of the receptor. Our focus is on the structural aspects of AF1 and how this flexible and disordered domain generates functional interactions with regulators of transcription. Our working hypothesis is that AR-AF1 domain exhibits induced folding when contacted by transcription regulators (such as TFIIF) into a more compact and ‘active’ conformation, enabling further co-regulator recruitment and ultimately transcription. Structural flexibility and intrinsic disorder of AR-AF1 were studied using predictive algorithms and fluorescence spectroscopy under different experimental conditions and the results revealed this domain retains characteristics indicative of molten-globule or pre-molten-globule-like structures. We hypothesize that this partially folded intermediate state is important for, and enables the AF1 domain to make, multiple protein–protein interactions. The structural aspects of AR-AF1 and interactions with TFIIF are discussed.

Structural Aspects of Protein–Protein Interactions

2021 ◽  
pp. 61-112
Author(s):  
Krishna Mohan Poluri ◽  
Khushboo Gulati ◽  
Sharanya Sarkar
Keyword(s):  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Structural Aspects

Protein-protein interactions of the p53 family with the Bcl-2 family in hepatocellular carcinoma

2011 ◽  
Vol 49 (08) ◽  
Author(s):  
LC König ◽  
M Meinhard ◽  
C Sandig ◽  
MH Bender ◽  
A Lovas ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
P53 Family

Partial Purification of a Specific Plasminogen Activator from Porcine Parotid Glands

1974 ◽  
Vol 31 (03) ◽  
pp. 403-414 ◽  
Author(s):  
Terence Cartwright
Keyword(s):  
Nucleic Acid ◽  
Salivary Glands ◽  
Plasminogen Activator ◽  
Protein Interactions ◽  
Partial Purification ◽  
Protein Protein Interactions ◽  
Parotid Glands ◽  
Two Stage ◽  
Preliminary Characterization ◽  
Specific Inhibitors

SummaryA method is described for the extraction with buffers of near physiological pH of a plasminogen activator from porcine salivary glands. Substantial purification of the activator was achieved although this was to some extent complicated by concomitant extraction of nucleic acid from the glands. Preliminary characterization experiments using specific inhibitors suggested that the activator functioned by a similar mechanism to that proposed for urokinase, but with some important kinetic differences in two-stage assay systems. The lack of reactivity of the pig gland enzyme in these systems might be related to the tendency to protein-protein interactions observed with this material.

Target-Templated de novo Design of Macrocyclic D-/L-Peptides: Inhibitors of the PD-1/PD-L1 Interaction

2020 ◽  
Author(s):  
Salvador Guardiola ◽  
Monica Varese ◽  
Xavier Roig ◽  
Jesús Garcia ◽  
Ernest Giralt
Keyword(s):  
Protein Interactions ◽  
Cyclic Peptides ◽  
General Framework ◽  
Large Scale ◽  
De Novo ◽  
Inhibitory Effect ◽  
Original Text ◽  
Protein Protein Interactions ◽  
Retraction Notice ◽  
Pharmaceutical Properties

<p>NOTE: This preprint has been retracted by consensus from all authors. See the retraction notice in place above; the original text can be found under "Version 1", accessible from the version selector above.</p><p><br></p><p>------------------------------------------------------------------------</p><p><br></p><p>Peptides, together with antibodies, are among the most potent biochemical tools to modulate challenging protein-protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing target-specific binders with improved pharmaceutical properties, such as macrocyclic peptides. Here we report a general framework that leverages the computational power of Rosetta for large-scale backbone sampling and energy scoring, followed by side-chain composition, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we identified two peptides (PD-<i>i</i>3 and PD-<i>i</i>6) that target PD-1, a key immune checkpoint, and work as protein ligand decoys. A comprehensive biophysical evaluation confirmed their binding mechanism to PD-1 and their inhibitory effect on the PD-1/PD-L1 interaction. Finally, elucidation of their solution structures by NMR served as validation of our <i>de novo </i>design approach. We anticipate that our results will provide a general framework for designing target-specific drug-like peptides.<i></i></p>

Target-Templated de novo Design of Macrocyclic D-/L-Peptides: Inhibitors of the PD-1/PD-L1 Interaction

2020 ◽  
Author(s):  
Salvador Guardiola ◽  
Monica Varese ◽  
Xavier Roig ◽  
Jesús Garcia ◽  
Ernest Giralt
Keyword(s):  
Protein Interactions ◽  
Cyclic Peptides ◽  
General Framework ◽  
Large Scale ◽  
De Novo ◽  
Inhibitory Effect ◽  
Original Text ◽  
Protein Protein Interactions ◽  
Retraction Notice ◽  
Pharmaceutical Properties

<p>NOTE: This preprint has been retracted by consensus from all authors. See the retraction notice in place above; the original text can be found under "Version 1", accessible from the version selector above.</p><p><br></p><p>------------------------------------------------------------------------</p><p><br></p><p>Peptides, together with antibodies, are among the most potent biochemical tools to modulate challenging protein-protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing target-specific binders with improved pharmaceutical properties, such as macrocyclic peptides. Here we report a general framework that leverages the computational power of Rosetta for large-scale backbone sampling and energy scoring, followed by side-chain composition, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we identified two peptides (PD-<i>i</i>3 and PD-<i>i</i>6) that target PD-1, a key immune checkpoint, and work as protein ligand decoys. A comprehensive biophysical evaluation confirmed their binding mechanism to PD-1 and their inhibitory effect on the PD-1/PD-L1 interaction. Finally, elucidation of their solution structures by NMR served as validation of our <i>de novo </i>design approach. We anticipate that our results will provide a general framework for designing target-specific drug-like peptides.<i></i></p>

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