Helix-helix interactions in membrane domains of bitopic proteins: Specificity and role of lipid environment

Bocharov, Eduard V.; Mineev, Konstantin S.; Павлов, Константин; Akimov, Sergey A.; Kuznetsov, Andrei; Efremov, Roman G.; Arseniev, Alexander S.

doi:10.1016/j.bbamem.2016.10.024

Cited by 89 publications

(107 citation statements)

References 184 publications

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“…In this concern, the boundary conditions of Eqs. (5,6) should be treated as an approximate, qualitative estimation of the boundary director jump. For this reason, we varied the numerical value of Δn as a parameter in order to qualitatively describe the free energy landscape of the system.…”

Section: Boundary Conditions For Membrane Inclusionsmentioning

confidence: 99%

Elastic deformations mediate interaction of the raft boundary with membrane inclusions leading to their effective lateral sorting

Pinigin

Kondrashov

Jiménez-Munguía

et al. 2020

Sci Rep

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Liquid-ordered lipid domains represent a lateral inhomogeneity in cellular membranes. these domains have elastic and physicochemical properties different from those of the surrounding membrane. in particular, their thickness exceeds that of the disordered membrane. thus, elastic deformations arise at the domain boundary in order to compensate for the thickness mismatch. in equilibrium, the deformations lead to an incomplete register of monolayer ordered domains: the elastic energy is minimal if domains in opposing monolayers lie on the top of each other, and their boundaries are laterally shifted by about 3 nm. This configuration introduces a region, composed of one ordered and one disordered monolayers, with an intermediate bilayer thickness. Besides, a jump in a local monolayer curvature takes place in this intermediate region, concentrating here most of the elastic stress. This region can participate in a lateral sorting of membrane inclusions by offering them an optimal bilayer thickness and local curvature conditions. In the present study, we consider the sorting of deformable lipid inclusions, undeformable peripheral and deeply incorporated peptide inclusions, and undeformable transmembrane inclusions of different molecular geometry. With rare exceptions, all types of inclusions have an affinity to the ordered domain boundary as compared to the bulk phases. the optimal lateral distribution of inclusions allows relaxing the elastic stress at the boundary of domains.Cellular membranes are laterally heterogeneous 1-3 . Many membrane proteins are believed to function properly only inside lipid-protein domains, also referred to as rafts 4-7 . Proteins in these domains are surrounded by a more or less thick lipid shell [8][9][10][11] . In model purely lipidic systems it is demonstrated that lipids can form similar domains, in which they are in a liquid-ordered (L o ) phase state, while the surrounding membrane is liquid-disordered (L d ) [12][13][14][15] . Ordered domains are usually bilayer, i.e. exist in both membrane leaflets at the same lateral position [14][15][16][17] . Such transbilayer coupling could be driven by elastic deformations arising at the domain boundary and by membrane thermal fluctuations 18-21 . The mechanism of this coupling is not specific to the exact lipid composition of the domain: only the higher ordering of lipids with respect to the surrounding membrane is important [22][23][24] . A bilayer structure of rafts is believed to be a key property in providing raft-dependent signal transduction across the plasma membrane 4,5 . There are increasing evidences that a raft interior itself may be laterally inhomogeneous: some molecules may prefer its boundary region rather than its bulk part. In particular, the fusion peptide of the human immunodeficiency virus (HIV) gp41 protein functions with the highest efficiency only in the presence of the L o /L d phase boundary in the target membrane 25,26 . In addition, the HIV receptor CCR5 preferentially localizes at the domain boundary 26 . It means t...

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Section: Boundary Conditions For Membrane Inclusionsmentioning

confidence: 99%

Elastic deformations mediate interaction of the raft boundary with membrane inclusions leading to their effective lateral sorting

Pinigin

Kondrashov

Jiménez-Munguía

et al. 2020

Sci Rep

Self Cite

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“…It is known that the EGFR dimer is formed through an interaction of the intracellular domain [38,48], the transmembrane domain [83,84], and the extracellular C-terminal region of Subdomain IV [58,62]. Indeed, the crystal structures of the intracellular domain show that the kinase domain dimer adopts a symmetric, back-to-back, inactive structure, stabilized by the AP-2 helices (Figure 2a) [63].…”

Section: Mechanism For Activation Of Egfr By Ligand Bindingmentioning

confidence: 99%

Activation of the EGF Receptor by Ligand Binding and Oncogenic Mutations: The “Rotation Model”

Purba

Saita

Maruyama

2017

Cells

145

123

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The epidermal growth factor receptor (EGFR) plays vital roles in cellular processes including cell proliferation, survival, motility, and differentiation. The dysregulated activation of the receptor is often implicated in human cancers. EGFR is synthesized as a single-pass transmembrane protein, which consists of an extracellular ligand-binding domain and an intracellular kinase domain separated by a single transmembrane domain. The receptor is activated by a variety of polypeptide ligands such as epidermal growth factor and transforming growth factor α. It has long been thought that EGFR is activated by ligand-induced dimerization of the receptor monomer, which brings intracellular kinase domains into close proximity for trans-autophosphorylation. An increasing number of diverse studies, however, demonstrate that EGFR is present as a pre-formed, yet inactive, dimer prior to ligand binding. Furthermore, recent progress in structural studies has provided insight into conformational changes during the activation of a pre-formed EGFR dimer. Upon ligand binding to the extracellular domain of EGFR, its transmembrane domains rotate or twist parallel to the plane of the cell membrane, resulting in the reorientation of the intracellular kinase domain dimer from a symmetric inactive configuration to an asymmetric active form (the “rotation model”). This model is also able to explain how oncogenic mutations activate the receptor in the absence of the ligand, without assuming that the mutations induce receptor dimerization. In this review, we discuss the mechanisms underlying the ligand-induced activation of the preformed EGFR dimer, as well as how oncogenic mutations constitutively activate the receptor dimer, based on the rotation model.

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“…Consequently, only the four remaining relative motions can occur: Moving toward or away from each other (which amounts to association or dissociation); moving perpendicular to the membrane plane (piston‐like motions); pivoting (also called scissoring or tilting); and finally rotation (gearbox‐like) . We note that the question of TM signaling by single pass proteins is widely discussed in the context of eukaryotic proteins, such as receptor tyrosine kinases …”

Section: Transmembrane Signaling: What Are the Possible Mechanisms?mentioning

confidence: 99%

Transmembrane Signal Transduction in Two‐Component Systems: Piston, Scissoring, or Helical Rotation?

Gushchin

Gordeliy

2017

BioEssays

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Allosteric and transmembrane (TM) signaling are among the major questions of structural biology. Here, we review and discuss signal transduction in four-helical TM bundles, focusing on histidine kinases and chemoreceptors found in two-component systems. Previously, piston, scissors, and helical rotation have been proposed as the mechanisms of TM signaling. We discuss theoretically possible conformational changes and examine the available experimental data, including the recent crystallographic structures of nitrate/nitrite sensor histidine kinase NarQ and phototaxis system NpSRII:NpHtrII. We show that TM helices can flex at multiple points and argue that the various conformational changes are not mutually exclusive, and often are observed concomitantly, throughout the TM domain or in its part. The piston and scissoring motions are the most prominent motions in the structures, but more research is needed for definitive conclusions.

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Helix-helix interactions in membrane domains of bitopic proteins: Specificity and role of lipid environment

Cited by 89 publications

References 184 publications

Elastic deformations mediate interaction of the raft boundary with membrane inclusions leading to their effective lateral sorting

Elastic deformations mediate interaction of the raft boundary with membrane inclusions leading to their effective lateral sorting

Activation of the EGF Receptor by Ligand Binding and Oncogenic Mutations: The “Rotation Model”

Transmembrane Signal Transduction in Two‐Component Systems: Piston, Scissoring, or Helical Rotation?

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