The Stability of Transmembrane Helix Interactions Measured in a Biological Membrane

2006 ◽  
Vol 358 (5) ◽  
pp. 1221-1228 ◽  
Author(s):  
Carmen Finger ◽  
Thomas Volkmer ◽  
Alexander Prodöhl ◽  
Daniel E. Otzen ◽  
Donald M. Engelman ◽  
...  
Keyword(s):  
Biological Membrane ◽  
Transmembrane Helix ◽  
The Stability ◽  
Helix Interactions

Specificity and promiscuity in membrane helix interactions

1994 ◽  
Vol 27 (2) ◽  
pp. 157-218 ◽  
Author(s):  
Mark A. Lemmon ◽  
Donald M. Engelman
Keyword(s):  
Membrane Proteins ◽  
Transmembrane Helix ◽  
Integral Membrane Proteins ◽  
Lipid Packing ◽  
Membrane Protein Folding ◽  
Membrane Spanning ◽  
Α Helix ◽  
Prosthetic Groups ◽  
Packing Effects ◽  
Helix Interactions

The membrane-spanning portions of many integral membrane proteins consist of one or a number of transmembrane α-helices, which are expected to be independently stable on thermodynamic grounds. Side-by-side interactions between these transmembrane α-helices are important in the folding and assembly of such integral membrane proteins and their complexes. In considering the contribution of these helix–helix interactions to membrane protein folding and oligomerization, a distinction between the energetics and specificity should be recognized. A number of contributions to the energetics of transmembrane helix association within the lipid bilayer will be relatively non-specific, including those resulting from charge–charge interactions and lipid–packing effects. Specificity (and part of the energy) in transmembrane α-helix association, however, appears to rely mainly upon a detailed stereochemical fit between sets of dynamically accessible states of particular helices. In some cases, these interactions are mediated in part by prosthetic groups.

scholarly journals NMR-based approach to measure the free energy of transmembrane helix–helix interactions

2014 ◽  
Vol 1838 (1) ◽  
pp. 164-172 ◽  
Author(s):  
Konstantin S. Mineev ◽  
Dmitry M. Lesovoy ◽  
Dinara R. Usmanova ◽  
Sergey A. Goncharuk ◽  
Mikhail A. Shulepko ◽  
...  
Keyword(s):  
Free Energy ◽  
Transmembrane Helix ◽  
Helix Interactions

Thrombin Modulates PAR1-PAR4 Heterodimers

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2203-2203 ◽  
Author(s):  
Maria de la Fuente ◽  
Amal Arachiche ◽  
Marvin T. Nieman
Keyword(s):  
Conflicts Of Interest ◽  
Transmembrane Helix ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Receptor Activation ◽  
Bimolecular Fluorescence Complementation ◽  
Physical Interaction ◽  
Signaling Specificity ◽  
C Terminus ◽  
The Stability

Abstract Abstract 2203 Thrombin is a potent platelet agonist. Thrombin activates platelets and other cells of the cardiovascular system by cleaving its receptors, protease activated receptor 1 (PAR1), PAR4 or both. PARs are G-protein coupled receptors that activate cellular signaling through Gq and G12/13. There is structural evidence that GPCRs, as a class, function as dimers and that dimerization can alter signaling specificity. Our previous studies have determined that PAR4 forms homodimers and have mapped the homodimer interface to transmembrane helix 4 (TM4). We have also shown that coexpression of PAR1 with PAR4 lowers the threshold for PAR4 activation by thrombin ∼10-fold. The purpose of the current study is to examine the physical interaction between PAR1 and PAR4 and how these interactions influence PAR1's ability to enhance PAR4 activation. The PAR1-PAR4 heterodimers were examined by bioluminescence resonance energy transfer (BRET) and bimolecular fluorescence complementation (BiFC). Similar to our previous studies with PAR4 homodimers, PAR1 homodimers were constitutive and did not require receptor activation. In contrast, PAR1-PAR4 heterodimers were not detected under basal conditions. However, when the cells were stimulated with 10 nM thrombin, we were able to detect a strong interaction between PAR1 and PAR4. We next examined if PAR1-PAR4 heterodimers would be induced by stimulating PAR1 or PAR4 individually with their agonist peptides TFLLRN (100 μM) or AYPGKF (500 μM), respectively. The agonist peptides were unable to induce heterodimers when added to the cells individually or simultaneously. These data demonstrate that PAR1 and PAR4 require allosteric changes induced by receptor cleavage by thrombin to mediate heterodimer formation. To examine this further, we removed 37 amino acids from the C-terminus of PAR1, which disrupts the eighth helix. The truncated PAR1 was able to form constitutive heterodimers with PAR4 and these heterodimers were unaffected by thrombin. These data suggest that PAR1 is the allosteric modulator of the PAR1-PAR4 heterodimers. Finally, the stability of the constitutive PAR1 and PAR4 homodimers was unchanged in response to thrombin or the agonist peptides. Taken together, these data suggest that PAR1 and PAR4 have a dynamic interaction depending on the context of their expression. Since PAR1 is an attractive antiplatelet target, the molecular interactions of this receptor on the cells surface must be taken into account when developing and characterizing these antagonists. Disclosures: No relevant conflicts of interest to declare.

Transformation of Liposomes: Mechanical Behavior and Stability

1993 ◽  
Vol 46 (11S) ◽  
pp. S289-S294
Author(s):  
D. Pamplona
Keyword(s):  
Critical Pressure ◽  
Fluid Layer ◽  
Biological Membrane ◽  
Finite Elasticity ◽  
Spherical Shape ◽  
Thin Shells ◽  
Side View ◽  
Front View ◽  
The Stability ◽  
Morphological Transformations

Liposomes are small artificial vesicles of lipid bilayer, wich enclose and are surrounded by water. Morphological transformations in liposomes, starting from a spherical shape, due to changes in the osmotic pressure, have been described in the literature. The first transformation is into a circular biconcave form, afterwards the biconcave side view is maintained, while the front view reveals transformations into elliptical or regular polygonal forms, usually triangular, square or pentagonal. Finite elasticity and the theory of thin shells were used to analyse the behavior of the liposomes under decreasing volume. The biological membrane was considered as a two dimensional fluid layer, exhibiting solid properties to some extent, e.g., elasticity. The stability of the liposmes was studied by using the method of elastic perturbation to obtain the critical pressure for the biconcave transformation and the long liposome tubes. The transformations to elliptical and regular polygonal forms were studied using the linear stability equations of elasticity.

scholarly journals The Affinity of GXXXG Motifs in Transmembrane Helix-Helix Interactions Is Modulated by Long-range Communication

2004 ◽  
Vol 279 (16) ◽  
pp. 16591-16597 ◽  
Author(s):  
Roman A. Melnyk ◽  
Sanguk Kim ◽  
A. Rachael Curran ◽  
Donald M. Engelman ◽  
James U. Bowie ◽  
...  
Keyword(s):  
Long Range ◽  
Transmembrane Helix ◽  
Long Range Communication ◽  
Helix Interactions

Sequence Context Modulates the Stability of a GxxxG-mediated Transmembrane Helix–Helix Dimer

2004 ◽  
Vol 341 (4) ◽  
pp. 991-998 ◽  
Author(s):  
Abigail K. Doura ◽  
Felix J. Kobus ◽  
Leonid Dubrovsky ◽  
Ellen Hibbard ◽  
Karen G. Fleming
Keyword(s):  
Transmembrane Helix ◽  
Sequence Context ◽  
The Stability
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