Track topics on Twitter Track topics that are important to you
Peripheral membrane proteins associate reversibly with biological membranes that, compared to protein binding partners, are structurally labile and devoid of specific binding pockets. Membranes in different subcellular compartments vary primarily in their chemical composition and physical properties, and recognition of these features is therefore critical for allowing such proteins to engage their proper membrane targets. Intrinsically disordered proteins are well-suited to accomplish this task using highly specific and low-to-moderate-affinity interactions governed by recognition principles that are both similar to and different from those that mediate the membrane interactions of rigid proteins. IDPs have also evolved multiple mechanisms to regulate membrane (and other) interactions and achieve their impressive functional diversity. Moreover, IDP-membrane interactions may have a kinetic advantage in fast processes requiring rapid control of such interactions, such as synaptic transmission or signaling. Herein we review the biophysics, regulation and functional implications of IDP-membrane interactions and include a brief overview of some of the methods that can be used to study such interactions. At each step, we use the example of alpha-synuclein, a protein involved in the pathogenesis of Parkinson's disease and one of the best characterized membrane-binding IDP, to illustrate some of the principles discussed.
This article was published in the following journal.
Name: Biochimica et biophysica acta. Proteins and proteomics
Electron paramagnetic resonance (EPR) spectroscopy in combination with site-directed spin labeling is ideally suited to study structure, dynamics, and interactions of intrinsically disordered proteins...
Alpha synuclein (αS) is a ~14 kDa intrinsically disordered protein. Decades of research have increased our knowledge on αS yet its physiological function remains largely elusive. The conversion of...
The recent discovery of biologically active fully disordered, so called random fuzzy protein-protein interactions leads to the question of how the high flexibility of these protein complexes correlate...
Alpha-synuclein oligomers are thought to be toxic mediators of Parkinson's disease and other alpha-synucleinopathies, but their histological detection in situ in diseased brain has been a challenge in...
In this issue of Structure, Peng et al. (2019) use a combination of computational modeling and solution-based experimental methods to characterize the intrinsically disordered N-terminal transactivat...
This is a Phase I clinical trial of the FDA approved drug Glycerol Phenylbutyrate to see if phenylbutyrate can increase the removal of alpha-synuclein from the brain into the bloodstream. ...
The main objectives are to determine on one hand whether oligomeric alpha-synuclein levels are increased in MSA patients compared to controls and on other hand whether there is a good agre...
The purpose of this study is to measure alpha-synuclein in peripheral body tissues and fluids in Parkinson's disease (PD). This may help in developing better treatments for PD patients in ...
Based on strong pre-clinical evidence of the effects of Nilotinib on neurodegenerative pathologies, including autophagic clearance of neurotoxic proteins, neurotransmitters (dopamine and g...
Parkinson's disease (PD) is the most frequent neurodegenerative disorder after Alzheimer's disease. It is characterized by motor symptoms (rigidity, tremor, slowness of movements), and non...
A synuclein that is closely related to ALPHA-SYNUCLEIN. It may play a neuroprotective role against some of the toxic effects of aggregated ALPHA-SYNUCLEIN.
Functional proteins that do not have unique, stable, folded, three-dimensional native structures or that possess non-ordered regions under physiological conditions. They are characterized by extraordinary structural flexibility and plasticity, which enable them to adopt different conformations in response to different stimuli or different interactions.
A homolog of ALPHA-SYNUCLEIN that plays a role in neurofilament network integrity. It is overexpressed in a variety of human NEOPLASMS and may be involved in modulating AXON architecture during EMBRYONIC DEVELOPMENT and in the adult. Gamma-Synuclein may also activate SIGNAL TRANSDUCTION PATHWAYS associated with ETS-DOMAIN PROTEIN ELK-1.
A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.
A ubiquitously expressed family of heterotrimeric GTP-binding protein alpha subunits that signal through interactions with a variety of second messengers as GTPASE-ACTIVATING PROTEINS; GUANINE NUCLEOTIDE EXCHANGE FACTORS; and HEAT SHOCK PROTEINS. The G12-G13 part of the name is also spelled G12/G13.
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...