Ligand binding to heme proteins: connection between dynamics and function

Biochemistry ◽  
1991 ◽  
Vol 30 (16) ◽  
pp. 3988-4001 ◽  
Author(s):  
Peter J. Steinbach ◽  
Anjum Ansari ◽  
Joel Berendzen ◽  
David Braunstein ◽  
Kelvin Chu ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Heme Proteins ◽  
Dynamics And Function ◽  
And Function

scholarly journals Control of Steroid Receptor Dynamics and Function by Genomic Actions of the Cochaperones p23 and Bag-1L

2014 ◽  
Vol 12 (1) ◽  
pp. nrs.12005 ◽  
Author(s):  
Laura Cato ◽  
Antje Neeb ◽  
Myles Brown ◽  
Andrew C. B. Cato
Keyword(s):  
Ligand Binding ◽  
Molecular Chaperones ◽  
Steroid Receptors ◽  
Steroid Receptor ◽  
Combined Effects ◽  
Receptor Dynamics ◽  
Receptor Action ◽  
Dynamics And Function ◽  
And Function ◽  
Receptor Turnover

Molecular chaperones encompass a group of unrelated proteins that facilitate the correct assembly and disassembly of other macromolecular structures of which they themselves do not remain a part. Chaperones associate with a large and diverse set of cofactors termed cochaperones that regulate their function and specificity. Chaperones and cochaperones regulate the activity of several classes of signaling molecules, including steroid receptors. Upon binding ligand, steroid receptors interact with discrete nucleotide sequences within the nucleus to control the expression of diverse physiological and developmental genes. Molecular chaperones and cochaperones are typically known to provide the correct conformation for ligand binding by the steroid receptors. While this contribution is widely accepted, recent studies have reported that they further modulate steroid receptor action outside ligand binding. Specifically, they are thought to contribute to receptor turnover, transport of the receptor to different subcellular localizations, recycling of the receptor on chromatin and stabilization of receptor DNA binding. In addition to these combined effects with molecular chaperones, cochaperones have additional functions that are independent of molecular chaperones, some of which impact steroid receptor action. Two well-studied examples are the cochaperones p23 and Bag-1L, which have been identified as modulators of steroid receptor activity in the nucleus. Understanding details of their regulatory action will provide new therapeutic opportunities for controlling steroid receptor action independent of the widespread effects of molecular chaperones.

scholarly journals Exploring the microbiome in health and disease

2017 ◽  
Vol 1 ◽  
pp. 239784731774188 ◽  
Author(s):  
Elena Scotti ◽  
Stéphanie Boué ◽  
Giuseppe Lo Sasso ◽  
Filippo Zanetti ◽  
Vincenzo Belcastro ◽  
...  
Keyword(s):  
Human Health ◽  
Metabolic Diseases ◽  
Skin Diseases ◽  
Human Microbiome ◽  
Chronic Obstructive ◽  
Microbial Composition ◽  
Obstructive Pulmonary Disease ◽  
New Findings ◽  
Dynamics And Function ◽  
And Function

The analysis of human microbiome is an exciting and rapidly expanding field of research. In the past decade, the biological relevance of the microbiome for human health has become evident. Microbiome comprises a complex collection of microorganisms, with their genes and metabolites, colonizing different body niches. It is now well known that the microbiome interacts with its host, assisting in the bioconversion of nutrients and detoxification, supporting immunity, protecting against pathogenic microbes, and maintaining health. Remarkable new findings showed that our microbiome not only primarily affects the health and function of the gastrointestinal tract but also has a strong influence on general body health through its close interaction with the nervous system and the lung. Therefore, a perfect and sensitive balanced interaction of microbes with the host is required for a healthy body. In fact, growing evidence suggests that the dynamics and function of the indigenous microbiota can be influenced by many factors, including genetics, diet, age, and toxicological agents like cigarette smoke, environmental contaminants, and drugs. The disruption of this balance, that is called dysbiosis, is associated with a plethora of diseases, including metabolic diseases, inflammatory bowel disease, chronic obstructive pulmonary disease, periodontitis, skin diseases, and neurological disorders. The importance of the host microbiome for the human health has also led to the emergence of novel therapeutic approaches focused on the intentional manipulation of the microbiota, either by restoring missing functions or eliminating harmful roles. In the present review, we outline recent studies devoted to elucidate not only the role of microbiome in health conditions and the possible link with various types of diseases but also the influence of various toxicological factors on the microbial composition and function.

scholarly journals Critical requirement of SOS1 RAS-GEF function for mitochondrial dynamics, metabolism, and redox homeostasis

Oncogene ◽  
2021 ◽  
Author(s):  
Rósula García-Navas ◽  
Pilar Liceras-Boillos ◽  
Carmela Gómez ◽  
Fernando C. Baltanás ◽  
Nuria Calzada ◽  
...  
Keyword(s):  
Mitochondrial Dynamics ◽  
Redox Homeostasis ◽  
Atp Production ◽  
Oxidative Energy Metabolism ◽  
Ras Activation ◽  
Mitochondrial Defects ◽  
Critical Requirement ◽  
Dynamics And Function ◽  
And Function ◽  
And Control

AbstractSOS1 ablation causes specific defective phenotypes in MEFs including increased levels of intracellular ROS. We showed that the mitochondria-targeted antioxidant MitoTEMPO restores normal endogenous ROS levels, suggesting predominant involvement of mitochondria in generation of this defective SOS1-dependent phenotype. The absence of SOS1 caused specific alterations of mitochondrial shape, mass, and dynamics accompanied by higher percentage of dysfunctional mitochondria and lower rates of electron transport in comparison to WT or SOS2-KO counterparts. SOS1-deficient MEFs also exhibited specific alterations of respiratory complexes and their assembly into mitochondrial supercomplexes and consistently reduced rates of respiration, glycolysis, and ATP production, together with distinctive patterns of substrate preference for oxidative energy metabolism and dependence on glucose for survival. RASless cells showed defective respiratory/metabolic phenotypes reminiscent of those of SOS1-deficient MEFs, suggesting that the mitochondrial defects of these cells are mechanistically linked to the absence of SOS1-GEF activity on cellular RAS targets. Our observations provide a direct mechanistic link between SOS1 and control of cellular oxidative stress and suggest that SOS1-mediated RAS activation is required for correct mitochondrial dynamics and function.

A naturally occurring Tyr143HisαIIb mutation abolishes αIIbβ3 function for soluble ligands but retains its ability for mediating cell adhesion and clot retraction: comparison with other mutations causing ligand-binding defects

Blood ◽  
2003 ◽  
Vol 101 (9) ◽  
pp. 3485-3491 ◽  
Author(s):  
Teruo Kiyoi ◽  
Yoshiaki Tomiyama ◽  
Shigenori Honda ◽  
Seiji Tadokoro ◽  
Morio Arai ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Ligand Binding ◽  
Binding Sites ◽  
Clot Retraction ◽  
Naturally Occurring ◽  
Binding Function ◽  
293 Cells ◽  
Ligand Binding Sites ◽  
Functional Defect ◽  
And Function

The molecular basis for the interaction between a prototypic non–I-domain integrin, αIIbβ3, and its ligands remains to be determined. In this study, we have characterized a novel missense mutation (Tyr143His) in αIIb associated with a variant of Glanzmann thrombasthenia. Osaka-12 platelets expressed a substantial amount of αIIbβ3(36%-41% of control) but failed to bind soluble ligands, including a high-affinity αIIbβ3-specific peptidomimetic antagonist. Sequence analysis revealed that Osaka-12 is a compound heterozygote for a single 521T>C substitution leading to a Tyr143His substitution in αIIb and for the null expression of αIIb mRNA from the maternal allele. Given that Tyr143 is located in the W3 4-1 loop of the β-propeller domain of αIIb, we examined the effects of Tyr143His or Tyr143Ala substitution on the expression and function of αIIbβ3 and compared them with KO (Arg-Thr insertion between 160 and 161 residues of αIIb) and with the Asp163Ala mutation located in the same loop by using 293 cells. Each of them abolished the binding function of αIIbβ3 for soluble ligands without disturbing αIIbβ3 expression. Because immobilized fibrinogen and fibrin are higher affinity/avidity ligands for αIIbβ3, we performed cell adhesion and clot retraction assays. In sharp contrast to KO mutation and Asp163AlaαIIbβ3, Tyr143HisαIIbβ3-expressing cells still had some ability for cell adhesion and clot retraction. Thus, the functional defect induced by Tyr143HisαIIb is likely caused by its allosteric effect rather than by a defect in the ligand-binding site itself. These detailed structure–function analyses provide better understanding of the ligand-binding sites in integrins.

scholarly journals Dynamics and function of compact nucleosome arrays

2009 ◽  
Vol 16 (9) ◽  
pp. 938-944 ◽  
Author(s):  
Michael G Poirier ◽  
Eugene Oh ◽  
Hannah S Tims ◽  
Jonathan Widom
Keyword(s):  
Dynamics And Function ◽  
And Function ◽  
Nucleosome Arrays

scholarly journals Dynamics and mechanism of ultrafast water–protein interactions

2016 ◽  
Vol 113 (30) ◽  
pp. 8424-8429 ◽  
Author(s):  
Yangzhong Qin ◽  
Lijuan Wang ◽  
Dongping Zhong
Keyword(s):  
Protein Interactions ◽  
Hydration Shell ◽  
Water Dynamics ◽  
Side Chain ◽  
Water Molecules ◽  
Ultrafast Dynamics ◽  
Hydration Water ◽  
Water Side ◽  
Dynamics And Function ◽  
And Function

Protein hydration is essential to its structure, dynamics, and function, but water–protein interactions have not been directly observed in real time at physiological temperature to our awareness. By using a tryptophan scan with femtosecond spectroscopy, we simultaneously measured the hydration water dynamics and protein side-chain motions with temperature dependence. We observed the heterogeneous hydration dynamics around the global protein surface with two types of coupled motions, collective water/side-chain reorientation in a few picoseconds and cooperative water/side-chain restructuring in tens of picoseconds. The ultrafast dynamics in hundreds of femtoseconds is from the outer-layer, bulk-type mobile water molecules in the hydration shell. We also found that the hydration water dynamics are always faster than protein side-chain relaxations but with the same energy barriers, indicating hydration shell fluctuations driving protein side-chain motions on the picosecond time scales and thus elucidating their ultimate relationship.

Does metformin modulate mitochondrial dynamics and function in type 2 diabetic patients?

2021 ◽  
Author(s):  
Aranzazu Martinez de Marañón ◽  
Francisco Gerardo Canet ◽  
Zaida Abad-Jimenez ◽  
Ana Jover ◽  
Carlos Morillas ◽  
...  
Keyword(s):  
Mitochondrial Dynamics ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Dynamics And Function ◽  
And Function ◽  
Type 2 Diabetic

Conformational stability, dynamics and function of human frataxin: Tryptophan side chain interplay

2021 ◽  
pp. 109086
Author(s):  
Lucía D. Espeche ◽  
Karl Ellioth Sewell ◽  
Ignacio H. Castro ◽  
Luciana Capece ◽  
María Florencia Pignataro ◽  
...  
Keyword(s):  
Conformational Stability ◽  
Side Chain ◽  
Dynamics And Function ◽  
Stability Dynamics ◽  
And Function
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