Abstract:
:The membrane-associated folding/unfolding of pH (low) insertion peptide (pHLIP) provides an opportunity to study how sequence variations influence the kinetics and pathway of peptide insertion into bilayers. Here, we present the results of steady-state and kinetics investigations of several pHLIP variants with different numbers of charged residues, with attached polar cargoes at the peptide's membrane-inserting end, and with three single-Trp variants placed at the beginning, middle, and end of the transmembrane helix. Each pHLIP variant exhibits a pH-dependent interaction with a lipid bilayer. Although the number of protonatable residues at the inserting end does not affect the ultimate formation of helical structure across a membrane, it correlates with the time for peptide insertion, the number of intermediate states on the folding pathway, and the rates of unfolding and exit. The presence of polar cargoes at the peptide's inserting end leads to the appearance of intermediate states on the insertion pathway. Cargo polarity correlates with a decrease of the insertion rate. We conclude that the existence of intermediate states on the folding and unfolding pathways is not mandatory and, in the simple case of a polypeptide with a noncharged and nonpolar inserting end, the folding and unfolding appears as an all-or-none transition. We propose a model for membrane-associated insertion/folding and exit/unfolding and discuss the importance of these observations for the design of new delivery agents for direct translocation of polar therapeutic and diagnostic cargo molecules across cellular membranes.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Karabadzhak AG,Weerakkody D,Wijesinghe D,Thakur MS,Engelman DM,Andreev OA,Markin VS,Reshetnyak YKdoi
10.1016/j.bpj.2012.03.021subject
Has Abstractpub_date
2012-04-18 00:00:00pages
1846-55issue
8eissn
0006-3495issn
1542-0086pii
S0006-3495(12)00332-3journal_volume
102pub_type
杂志文章abstract::Characterizing the ionic distribution around chromatin is important for understanding the electrostatic forces governing chromatin structure and function. Here we develop an electrostatic model to handle multivalent ions and compute the ionic distribution around a mesoscale chromatin model as a function of conformatio...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2010.08.023
更新日期:2010-10-20 00:00:00
abstract::Lateral tension in cell plasma membranes plays an essential role in regulation of a number of membrane-related intracellular processes and cell motion. Understanding the physical factors generating the lateral tension and quantitative determination of the tension distribution along the cell membrane is an emerging top...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2013.11.009
更新日期:2014-01-07 00:00:00
abstract::Investigations into the spatiotemporal dynamics of DNA repair using live-cell imaging are aided by the ability to generate well defined regions of ultravioletlike photolesions in an optical microscope. We demonstrate that multiphoton excitation of DNA in live cells with visible femtosecond pulses produces thymine cycl...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2011.09.031
更新日期:2011-11-02 00:00:00
abstract::The viral genome and replicative enzymes of the human immunodeficiency virus are encased in a shell consisting of assembled mature capsid protein (CA). The core shell is a stable, effective protective barrier, but is also poised for dissolution on cue to allow transmission of the viral genome into its new host. In thi...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(01)75725-6
更新日期:2001-07-01 00:00:00
abstract::The theory of the electromagnetic blood flow measuring technique is extended from the well known case (conductive liquid flowing through an insulating tube) to more realistic situations. First the conductivity of the vessel is taken into account, and the electric potentials in both liquid and vessel wall are calculate...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/s0006-3495(61)86912-9
更新日期:1961-11-01 00:00:00
abstract::To assay cell cycle progression in synchronized culture of yeast we have applied dielectric spectroscopy to its real-time monitoring. The dielectric monitoring is based on the electromagnetic induction method, regarded as a nonelectrode method, which has resolved the problems encountered in measurements with metal ele...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(99)77487-4
更新日期:1999-06-01 00:00:00
abstract::39K nuclear magnetic resonance (NMR) spectra were readily obtained, in vivo, from rat muscle, kidney, and brain in 5-10 min with signal-to-noise ratios of approximately 20:1. Quantitation of the K+ signal was achieved by reference to an external standard of KCl/dysprosium nitrate as well as by reference to the proton ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(87)83332-5
更新日期:1987-02-01 00:00:00
abstract::The effect of antibodies to glycophorin A on the rotational diffusion of band 3 in human erythrocyte membranes was investigated by transient dichrosim. Three antibodies that recognize different epitopes on the exofacial domain of glycophorin A all strongly reduce the rotational mobility of band 3. The effect is at mos...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(95)80365-6
更新日期:1995-05-01 00:00:00
abstract::Based on experimental evidence for 2D array formation of bacteriorhodopsin, we propose a general model for lipid-mediated 2D array formation of membrane proteins in lipid bilayers. The model includes two different lipid species, "annular" lipids and "neutral" lipids, and one protein species. The central assumption of ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(98)74037-8
更新日期:1998-09-01 00:00:00
abstract::RNA functions are often kinetically controlled. The folding kinetics of RNAs involves global structural changes and local nucleotide movement, such as base flipping. The most elementary step in RNA folding is the closing and opening of a basepair. By integrating molecular dynamics simulation, master equation, and kine...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2019.09.017
更新日期:2019-11-05 00:00:00
abstract::Far infrared (FIR) spectral measurements of wild-type (WT) and D96N mutant bacteriorhodopsin thin films have been carried out using terahertz time domain spectroscopy as a function of hydration, temperature, and conformational state. The results are compared to calculated spectra generated via normal mode analyses usi...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(03)74562-7
更新日期:2003-08-01 00:00:00
abstract::Hybrid global optimization methods attempt to combine the beneficial features of two or more algorithms, and can be powerful methods for solving challenging nonconvex optimization problems. In this paper, novel classes of hybrid global optimization methods, termed alternating hybrids, are introduced for application as...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(03)74905-4
更新日期:2003-02-01 00:00:00
abstract::The cellular cytoplasm is a complex, heterogeneous environment (both spatially and temporally) that exhibits viscoelastic behavior. To further develop our quantitative insight into cellular transport, we analyze data sets of mRNA molecules fluorescently labeled with MS2-GFP tracked in real time in live Escherichia col...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2016.11.3208
更新日期:2017-02-07 00:00:00
abstract::The role played by non-homogeneous interactions in stabilizing cooperative structural changes in proteins was investigated by exhaustive simulations of all compact conformations compatible with several well-defined globule-like shapes in three dimensions. Conformational free energies corresponding to the association o...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/s0006-3495(94)80798-2
更新日期:1994-02-01 00:00:00
abstract::By considering how polymer structures are distributed in conformation space, we show that it is possible to quantify the difficulty of structural prediction and to provide a measure of progress for prediction calculations. The critical issue is the probability that a conformation is found within a specified distance o...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.104.041723
更新日期:2004-07-01 00:00:00
abstract::We report evidence for an unconventional type of allosteric regulation of a biomotor. We show that the genome-packaging motor of phage ϕ29 is regulated by a sensor that detects the density and conformation of the DNA packaged inside the viral capsid, and slows the motor by a mechanism distinct from the effect of a dir...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2014.11.3469
更新日期:2015-01-20 00:00:00
abstract::Potentiometric titrations and surface potential measurements have been used to determine the intrinsic pKa values of both the carboxyl and amino groups of phosphatidylserine (PS) in mixed vesicles of PS and phosphatidylcholine (PC), and also of the amino group of phosphatidylethanolamine (PE) in mixed PE-PC vesicles. ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(86)83655-4
更新日期:1986-02-01 00:00:00
abstract::Multiplex hybridization reactions of perfectly matched duplexes and duplexes containing a single basepair mismatch (SNPs) were investigated on DNA microarrays. Effects of duplex length, G-C percentage, and relative position of the SNP on duplex hybridization and SNP resolution were determined. Our theoretical model of...
journal_title:Biophysical journal
pub_type: 信件
doi:10.1529/biophysj.107.105320
更新日期:2007-05-15 00:00:00
abstract::Forces between type I collagen triple helices are studied in solvents of varying hydrogen-bonding ability. The swelling of collagen fibers in reconstituted films is controlled by the concentration of soluble polymers that are excluded from the fibers and that compete osmotically with collagen for available solvent. Th...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(97)78674-0
更新日期:1997-01-01 00:00:00
abstract::A previously established multiscale population genetics model posits that fitness can be inferred from the physical properties of proteins under the physiological assumption that a loss of stability by any protein confers the lethal phenotype to an organism. Here, we develop this model further by positing that replica...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2009.11.048
更新日期:2010-04-07 00:00:00
abstract::Adenylate kinase, an enzyme that catalyzes the phosphoryl transfer between ATP and AMP, can interconvert between the open and catalytically potent (closed) forms even without binding ligands. Several aspects of the enzyme elasticity and internal dynamics are analyzed here by atomistic molecular dynamics simulations co...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.108.135467
更新日期:2008-12-15 00:00:00
abstract::Crystals have been grown of "sperm whale" myoglobin produced in Escherichia coli from a synthetic gene and the structure has been solved to 1.9 A resolution. Because of a remaining initiator methionine, this protein crystallizes in a different space group from native sperm whale myoglobin. The three-dimensional struct...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(90)82540-6
更新日期:1990-02-01 00:00:00
abstract::Synchrotron x-ray scattering measurements were performed on dilute solutions of the purified hemocyanin subunit (Bsin1) from scorpion (Buthus sindicus) and the N-terminal functional unit (Rta) from a marine snail (Rapana thomasiana). The model-independent approach based on spherical harmonics was applied to calculate ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/s0006-3495(00)76655-0
更新日期:2000-02-01 00:00:00
abstract::The partial specific volume and adiabatic compressibility of proteins reflect the hydration properties of the solvent-exposed protein surface, as well as changes in conformational states. Reverse micelles, or water-in-oil microemulsions, are protein-sized, optically-clear microassemblies in which hydration can be expe...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(01)76243-1
更新日期:2001-06-01 00:00:00
abstract::The electric quadrupole moment of the deuterium nucleus provides a nuclear magnetic resonance (NMR) probe of electric field gradients, and thereby of organization of tissue water. 8-17% of H(2)O in rat muscle and brain was replaced by D(2)O from 50% deuterated drinking water. The peak height of the steady-state NMR sp...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(69)86388-5
更新日期:1969-03-01 00:00:00
abstract::Cholesterol, due to its condensing effect, is considered an important regulator of membrane thickness. Other sterols, due to their structural similarities to cholesterol, are often assumed to have a universal effect on membrane properties similar to the condensing effect of cholesterol, albeit possibly to different de...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2016.04.003
更新日期:2016-05-10 00:00:00
abstract::The partition coefficients (K(P)) of a series of single-chain and double-chain fluorescent amphiphiles, between solid ordered (P(beta') and L(beta)) and liquid disordered (L(alpha) of the type l(d)) lipid phases coexisting in the same lipid bilayer, was studied using steady-state fluorescence emission anisotropy. The ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(00)76840-8
更新日期:2000-06-01 00:00:00
abstract::Atrial fibrosis has been implicated in the development and maintenance of atrial arrhythmias, and is characterized by expansion of the extracellular matrix and an increased number of fibroblasts (Fbs). Electrotonic coupling between atrial myocytes and Fbs may contribute to the formation of an arrhythmogenic substrate....
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2009.07.054
更新日期:2009-10-21 00:00:00
abstract::Staphylococcus aureus expresses numerous virulence factors that aid in immune evasion. The four-domain staphylococcal immunoglobulin binding (Sbi) protein interacts with complement component 3 (C3) and its thioester domain (C3d)-containing fragments. Recent structural data suggested two possible modes of binding of Sb...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2014.01.033
更新日期:2014-03-04 00:00:00
abstract::Glucagon solutions at pH 2.0 were subjected to mechanical agitation at 37 degrees C in the presence of a hydrophobic surface to explore the details of aggregation and fiber formation. High-resolution intermittent-contact atomic force microscopy performed in solution revealed the presence of aggregates after 0.5 h; how...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.105.077438
更新日期:2006-09-01 00:00:00