Design of Bioelectronic Interfaces by Exploiting Hinge-Bending Motions in Proteins

Science ◽  
2001 ◽  
Vol 293 (5535) ◽  
pp. 1641-1644 ◽  
Author(s):  
D. E. Benson
Keyword(s):  
1982 ◽  
Vol 257 (3) ◽  
pp. 1131-1133 ◽  
Author(s):  
B. Mao ◽  
M.R. Pear ◽  
J.A. McCammon ◽  
F.A. Quiocho

1983 ◽  
Vol 16 (1) ◽  
pp. 42-46 ◽  
Author(s):  
O. Glatter ◽  
P. Laggner

The possibilities of obtaining structural information from X-ray small-angle scattering experiments with `white' polychromatic synchrotron radiation using line collimation are investigated by numerical simulation. Theoretical scattering curves of geometrical models were smeared with the appropriate wavelength distributions and slit-length functions, afflicted by statistical noise, and then evaluated by identical methods as normally used for experimental data, as described previously [program ITP; Glatter (1977). J. Appl. Cryst. 10, 415–421]. It is shown that even for a wavelength distribution of 50% half width, the information content is not limited to the parameters derived from the central part of the scattering curves, i.e. the radius of gyration and the zero-angle intensity, but also allows qualitative information on particle shape via the distance distribution function p(r). By a `hinge-bending model' consisting of two cylinders linked together at different angles it is demonstrated that changes in the radius of gyration amounting to less than 5% can be detected and quantified, and the qualitative changes in particle shape be reproduced.


2013 ◽  
Vol 289 (3) ◽  
pp. 1798-1814 ◽  
Author(s):  
Christopher J. Yates ◽  
Geoffrey Masuyer ◽  
Sylva L. U. Schwager ◽  
Mohd Akif ◽  
Edward D. Sturrock ◽  
...  

Somatic angiotensin-converting enzyme (sACE), a key regulator of blood pressure and electrolyte fluid homeostasis, cleaves the vasoactive angiotensin-I, bradykinin, and a number of other physiologically relevant peptides. sACE consists of two homologous and catalytically active N- and C-domains, which display marked differences in substrate specificities and chloride activation. A series of single substitution mutants were generated and evaluated under varying chloride concentrations using isothermal titration calorimetry. The x-ray crystal structures of the mutants provided details on the chloride-dependent interactions with ACE. Chloride binding in the chloride 1 pocket of C-domain ACE was found to affect positioning of residues from the active site. Analysis of the chloride 2 pocket R522Q and R522K mutations revealed the key interactions with the catalytic site that are stabilized via chloride coordination of Arg522. Substrate interactions in the S2 subsite were shown to affect chloride affinity in the chloride 2 pocket. The Glu403-Lys118 salt bridge in C-domain ACE was shown to stabilize the hinge-bending region and reduce chloride affinity by constraining the chloride 2 pocket. This work demonstrated that substrate composition to the C-terminal side of the scissile bond as well as interactions of larger substrates in the S2 subsite moderate chloride affinity in the chloride 2 pocket of the ACE C-domain, providing a rationale for the substrate-selective nature of chloride dependence in ACE and how this varies between the N- and C-domains.


2012 ◽  
Vol 1818 (9) ◽  
pp. 2120-2125 ◽  
Author(s):  
Annika F. Barber ◽  
Vincenzo Carnevale ◽  
S.G. Raju ◽  
Cristiano Amaral ◽  
Werner Treptow ◽  
...  

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Chloé Habermacher ◽  
Adeline Martz ◽  
Nicolas Calimet ◽  
Damien Lemoine ◽  
Laurie Peverini ◽  
...  

P2X receptors function by opening a transmembrane pore in response to extracellular ATP. Recent crystal structures solved in apo and ATP-bound states revealed molecular motions of the extracellular domain following agonist binding. However, the mechanism of pore opening still remains controversial. Here we use photo-switchable cross-linkers as ‘molecular tweezers’ to monitor a series of inter-residue distances in the transmembrane domain of the P2X2 receptor during activation. These experimentally based structural constraints combined with computational studies provide high-resolution models of the channel in the open and closed states. We show that the extent of the outer pore expansion is significantly reduced compared to the ATP-bound structure. Our data further reveal that the inner and outer ends of adjacent pore-lining helices come closer during opening, likely through a hinge-bending motion. These results provide new insight into the gating mechanism of P2X receptors and establish a versatile strategy applicable to other membrane proteins.


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