Swimming through the hydrophobic sea: New insights in protein translocation

Mindell, Joseph A.

doi:10.1073/pnas.95.8.4081

Cited by 3 publications

(3 citation statements)

References 13 publications

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“…The interplay of hydrophobicity and electrostatics and their distribution within the polypeptide sequence have only been studied in detail for small peptides (3-5, 7, 13-15, 17-20). In the case of proteins, the role of these effects on the association with and the insertion into membranes are still poorly understood (2,(21)(22)(23)(24).The study of the membrane insertion process of the translocation (T) 1 domain of diphtheria toxin (25) can provide precious insight into the interactions between proteins and membranes and the refolding mechanisms of membrane proteins. During intoxication of cells (25), the toxin reaches the early endosomes through the clathrin-coated pathway (26).…”

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Membrane Protein Insertion Regulated by Bringing Electrostatic and Hydrophobic Interactions into Play

Chenal

Savarin

Nizard

et al. 2002

Journal of Biological Chemistry

153

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The study of the membrane insertion of the translocation domain of diphtheria toxin deepens our insight into the interactions between proteins and membranes. During cell intoxication, this domain undergoes a change from a soluble and folded state at alkaline pH to a functional membrane-inserted state at acid pH. We found that hydrophobic and electrostatic interactions occur in a sequential manner between the domain and the membrane during the insertion. The first step involves hydrophobic interactions by the C-terminal region. This is because of the pH-induced formation of a molten globule specialized for binding to the membrane. Accumulation of this molten globule follows a precise molecular mechanism adapted to the toxin function. The second step, as the pH decreases, leads to the functional inserted state. It arises from the changes in the balance of electrostatic attractions and repulsions between the N-terminal part and the membrane. Our study shows how the structural changes and the interaction with membranes of the translocation domain are finely tuned by pH changes to take advantage of the cellular uptake system.Folding and insertion of membrane proteins (1, 2), binding of hormones to membrane receptors (3), action of antibiotic peptides (4, 5), protein translocation, and internalization of toxins (6) are examples of phenomena that require the interactions of polypeptide chains with membranes. Because of the anisotropic nature of membranes, the initial steps of the association and the final structure and localization of polypeptide chains within membranes depend on a combination of hydrophobic and electrostatic interactions (7). Hydrophobic interactions are dominant for the insertion of transmembrane polypeptides. Electrostatic interactions are important for the binding of antibiotic peptides (5,8), the association of proteins with the surface of the membrane (9 -11), and as determinants of the topology of integral membrane proteins after biosynthesis (12). In most cases, electrostatic interactions are the result of the attraction between anionic phospholipid head groups and basic amino acid side chains (13,14). However, there are examples where electrostatic repulsions are involved in the membrane association of peptides, particularly when their structure and localization within the membrane is regulated by the pH (15-19). The interplay of hydrophobicity and electrostatics and their distribution within the polypeptide sequence have only been studied in detail for small peptides (3-5, 7, 13-15, 17-20). In the case of proteins, the role of these effects on the association with and the insertion into membranes are still poorly understood (2,(21)(22)(23)(24).The study of the membrane insertion process of the translocation (T) 1 domain of diphtheria toxin (25) can provide precious insight into the interactions between proteins and membranes and the refolding mechanisms of membrane proteins. During intoxication of cells (25), the toxin reaches the early endosomes through the clathrin-coated pathway (26). Beca...

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confidence: 99%

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confidence: 99%

Membrane Protein Insertion Regulated by Bringing Electrostatic and Hydrophobic Interactions into Play

Chenal

Savarin

Nizard

et al. 2002

Journal of Biological Chemistry

153

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“…Export and import of proteins by cells and intracellular organelles of eukaryotes are ubiquitous (see Mindell [1221] for a nice biblical analogy). These processes are carried out by protein translocation motors (also called translocases and translocons) [1222,1223,1224,1225,1226] which use input energy to drive their operation [1227].…”

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confidence: 99%

Stochastic mechano-chemical kinetics of molecular motors: a multidisciplinary enterprise from a physicist's perspective

Chowdhury

2012

Preprint

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A molecular motor is made of either a single macromolecule or a macromolecular complex. Just like their macroscopic counterparts, molecular motors "transduce" input energy into mechanical work. All the nanomotors considered here operate under isothermal conditions far from equilibrium. Moreover, one of the possible mechanisms of energy transduction, called Brownian ratchet, does not even have any macroscopic counterpart. But, molecular motor is not synonymous with Brownian ratchet; a large number of molecular motors execute a noisy power stroke, rather than operating as Brownian ratchet. We review not only the structural design and stochastic kinetics of individual single motors, but also their coordination, cooperation and competition as well as the assembly of multimodule motors in various intracellular kinetic processes. Although all the motors considered here execute mechanical movements, efficiency and power output are not necessarily good measures of performance of some motors. Among the intracellular nano-motors, we consider the porters, sliders and rowers, pistons and hooks, exporters, importers, packers and movers as well as those that also synthesize, manipulate and degrade "macromolecules of life". We review mostly the quantitative models for the kinetics of these motors. We also describe several of those motordriven intracellular stochastic processes for which quantitative models are yet to be developed. In part I, we discuss mainly the methodology and the generic models of various important classes of molecular motors. In part II, we review many specific examples emphasizing the unity of the basic mechanisms as well as diversity of operations arising from the differences in their detailed structure and kinetics. Multi-disciplinary research is presented here from the perspective of physicists.

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Stochastic mechano-chemical kinetics of molecular motors: A multidisciplinary enterprise from a physicist’s perspective

2013

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Swimming through the hydrophobic sea: New insights in protein translocation

Cited by 3 publications

References 13 publications

Membrane Protein Insertion Regulated by Bringing Electrostatic and Hydrophobic Interactions into Play

Membrane Protein Insertion Regulated by Bringing Electrostatic and Hydrophobic Interactions into Play

Stochastic mechano-chemical kinetics of molecular motors: a multidisciplinary enterprise from a physicist's perspective

Stochastic mechano-chemical kinetics of molecular motors: A multidisciplinary enterprise from a physicist’s perspective

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