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Molecular and Functional Characterizations of Protein-protein Interactions in Central Nervous System

Molecular and Functional Characterizations of Protein-protein Interactions in Central Nervous System PDF Author: Min Wang
Publisher:
ISBN: 9780494776711
Category :
Languages : en
Pages : 406

Book Description
Many pathological processes are associated with excessive neurotransmitter release that leads to the over-stimulation of post-synaptic neurotransmitter receptors. Examples include excessive activation of glutamate receptors in ischemic stroke and hyper-dopaminergic state in schizophrenia and drug addiction. Thus, it would seem that simply antagonizing the involved receptors should be able to correct the pathological condition. In some instances, this strategy has been somewhat effective, such as with the use of dopamine D2 receptor antagonists as antipsychotics in the treatment of positive symptoms of schizophrenia despite severe side effect. However, clinical application of drugs antagonizing glutamate receptor in the treatment of stoke, although attracting intensive research effort, has been restricted by serious side effects caused by suppressing postsynaptic responses that are needed for normal brain function. As a consequence, it is important to develop novel therapeutics aiming at specific targets with minimized side effects. Numerous studies have suggested that the pathophysiology of neuropsychiatric disorders, drug addictions and stroke involves multiple neurotransmitter receptor systems such as the dopamine and glutamate systems. The activation or inhibition of one receptor can have cross-functional effect that will be better understood by investigating the functional and structural relationship between receptor systems. Thus, the present study has focused on characterizing receptor-receptor interactions associated with dopamine receptors and glutamate receptors, and to elucidate the physiological and pathological consequence of altered receptor interactions in schizophrenia, depression and ischemic stroke.

Molecular and Functional Characterizations of Protein-protein Interactions in Central Nervous System

Molecular and Functional Characterizations of Protein-protein Interactions in Central Nervous System PDF Author: Min Wang
Publisher:
ISBN: 9780494776711
Category :
Languages : en
Pages : 406

Book Description
Many pathological processes are associated with excessive neurotransmitter release that leads to the over-stimulation of post-synaptic neurotransmitter receptors. Examples include excessive activation of glutamate receptors in ischemic stroke and hyper-dopaminergic state in schizophrenia and drug addiction. Thus, it would seem that simply antagonizing the involved receptors should be able to correct the pathological condition. In some instances, this strategy has been somewhat effective, such as with the use of dopamine D2 receptor antagonists as antipsychotics in the treatment of positive symptoms of schizophrenia despite severe side effect. However, clinical application of drugs antagonizing glutamate receptor in the treatment of stoke, although attracting intensive research effort, has been restricted by serious side effects caused by suppressing postsynaptic responses that are needed for normal brain function. As a consequence, it is important to develop novel therapeutics aiming at specific targets with minimized side effects. Numerous studies have suggested that the pathophysiology of neuropsychiatric disorders, drug addictions and stroke involves multiple neurotransmitter receptor systems such as the dopamine and glutamate systems. The activation or inhibition of one receptor can have cross-functional effect that will be better understood by investigating the functional and structural relationship between receptor systems. Thus, the present study has focused on characterizing receptor-receptor interactions associated with dopamine receptors and glutamate receptors, and to elucidate the physiological and pathological consequence of altered receptor interactions in schizophrenia, depression and ischemic stroke.

Single Molecular and Computational Characterizations of Functional Protein Interactions

Single Molecular and Computational Characterizations of Functional Protein Interactions PDF Author: Amy Davenport Migliori
Publisher:
ISBN: 9781303687983
Category :
Languages : en
Pages : 139

Book Description
Often, proteins are studied using bulk techniques, in which the average properties of large ensembles of molecules are studied. Although this has led to substantial new knowledge, the use of single-molecule biophysics and computational techniques to understand individual molecular actions and dynamics and the role of each residue allows for a more complete picture of activity in some cases. We present two applications of such techniques, first to determine the relationship between structure and function of the DNA translocation motor gp17 in Bacteriophage T4, and second to study looping of DNA mediated by the tumor suppressor protein p53. Specifically, we studied the role of an interface between the N- and C-terminal subdomains in generation of the high packaging forces and translocation velocities using a dual-beam optical trap. Mutation of charged amino acids located within this interface region confirmed that electrostatic forces play a role in force and velocity generation, with mutants showing a reduction in forward velocity, average velocity, and percentage of time spent packaging at different applied forces. To explain these experimental results, we generated a two-state computational model to calculate the free energy of the translocation step in gp17. We found excellent correlation between experimental data and calculated free energy change of translocation. Decomposition of the free energy change allowed for the identification of key residues involved in gp17-mediated packaging, and the role of each was explained. These results reveal that the power stroke of the motor requires substantial contributions from charged residues, hydrophobic residues, and polar residues instead of charged residues alone. Finally, we propose that several of these key residues may be hot spot residues, contributing a significant portion of the free energy used to package DNA. p53-mediated loop formation in DNA was studied using direct measurement with a dual optical tweezer setup. Looping of DNA by p53 has previously been demonstrated qualitatively using cryo-electron microscopy as well as transcription assays. we demonstrated formation of loops in purified human Col18A promoter containing five p53 binding sites. This looping may be directly related to p53 activity at transcriptional start sites.

Protein-Protein Interaction Networks

Protein-Protein Interaction Networks PDF Author: Stefan Canzar
Publisher: Humana
ISBN: 9781493998722
Category : Science
Languages : en
Pages : 0

Book Description
This volume explores techniques that study interactions between proteins in different species, and combines them with context-specific data, analysis of omics datasets, and assembles individual interactions into higher-order semantic units, i.e., protein complexes and functional modules. The chapters in this book cover computational methods that solve diverse tasks such as the prediction of functional protein-protein interactions; the alignment-based comparison of interaction networks by SANA; using the RaptorX-ComplexContact webserver to predict inter-protein residue-residue contacts; the docking of alternative confirmations of proteins participating in binary interactions and the visually-guided selection of a docking model using COZOID; the detection of novel functional units by KeyPathwayMiner and how PathClass can use such de novo pathways to classify breast cancer subtypes. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary hardware- and software, step-by-step, readily reproducible computational protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and comprehensive, Protein-Protein Interaction Networks: Methods and Protocols is a valuable resource for both novice and expert researchers who are interested in learning more about this evolving field.

Molecular Biology of The Cell

Molecular Biology of The Cell PDF Author: Bruce Alberts
Publisher:
ISBN: 9780815332183
Category : Cytology
Languages : en
Pages : 0

Book Description


Serotonin Receptors in Neurobiology

Serotonin Receptors in Neurobiology PDF Author: Amitabha Chattopadhyay
Publisher: CRC Press
ISBN: 1420005758
Category : Medical
Languages : en
Pages : 230

Book Description
A number of developments spanning a multitude of techniques makes this an exciting time for research in serotonin receptors. A comprehensive review of the subject from a multidisciplinary perspective, Serotonin Receptors in Neurobiology is among the first books to include information on serotonin receptor knockout studies. With contributions from l

Perspectives in Ecological Theory

Perspectives in Ecological Theory PDF Author: Ramón Margalef
Publisher:
ISBN:
Category : Science
Languages : en
Pages : 128

Book Description
The ecosystem as a cybernetic system. Ecological succession and exploitation by man. The study of pelagic ecosystems. Evolution in the frame of ecosystem organization.

Receptor-Receptor Interactions

Receptor-Receptor Interactions PDF Author: Kjell Fuxe
Publisher: Springer Science & Business Media
ISBN: 1468454153
Category : Computers
Languages : en
Pages : 577

Book Description


Protein Dimerization and Oligomerization in Biology

Protein Dimerization and Oligomerization in Biology PDF Author: Jacqueline M. Matthews
Publisher: Springer Science & Business Media
ISBN: 1461432294
Category : Medical
Languages : en
Pages : 184

Book Description
This volume has a strong focus on homo-oligomerization, which is surprisingly common. However, protein function is so often linked to both homo- and hetero-oligomerization and many heterologous interactions likely evolved from homologous interaction, so this volume also covers many aspects of hetero-oligomerization.

Anatomy and Physiology

Anatomy and Physiology PDF Author: J. Gordon Betts
Publisher:
ISBN: 9781947172807
Category :
Languages : en
Pages : 0

Book Description


Macromolecular Protein Complexes III: Structure and Function

Macromolecular Protein Complexes III: Structure and Function PDF Author: J. Robin Harris
Publisher: Springer Nature
ISBN: 3030589714
Category : Science
Languages : en
Pages : 580

Book Description
This book covers important topics such as the dynamic structure and function of the 26S proteasome, the DNA replication machine: structure and dynamic function and the structural organization and protein–protein interactions in the human adenovirus capsid, to mention but a few. The 18 chapters included here, written by experts in their specific field, are at the forefront of scientific knowledge. The impressive integration of structural data from X-ray crystallography with that from cryo-electron microscopy is apparent throughout the book. In addition, functional aspects are also given a high priority. Chapter 1 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.