scholarly journals Role of the hydrophobic and charged residues in the 218–226 region of apoA-I in the biogenesis of HDL

2013 ◽  
Vol 54 (12) ◽  
pp. 3281-3292 ◽  
Author(s):  
Panagiotis Fotakis ◽  
Andreas K. Kateifides ◽  
Christina Gkolfinopoulou ◽  
Dimitra Georgiadou ◽  
Melissa Beck ◽  
...  
Keyword(s):  
Charged Residues

scholarly journals Functional Role of Charged Residues in the Transmembrane Segments of the Yeast Plasma Membrane H+-ATPase

2000 ◽  
Vol 275 (21) ◽  
pp. 15709-15716 ◽  
Author(s):  
Valery V. Petrov ◽  
Kristine P. Padmanabha ◽  
Robert K. Nakamoto ◽  
Kenneth E. Allen ◽  
Carolyn W. Slayman
Keyword(s):  
Plasma Membrane ◽  
Functional Role ◽  
Yeast Plasma Membrane ◽  
Transmembrane Segments ◽  
Charged Residues

Role of S4 positively charged residues in the regulation of Kv4.3 inactivation and recovery

2007 ◽  
Vol 293 (3) ◽  
pp. C906-C914 ◽  
Author(s):  
Matthew R. Skerritt ◽  
Donald L. Campbell
Keyword(s):  
Positive Charge ◽  
Voltage Sensitivity ◽  
Shaker Channels ◽  
Recovery From Inactivation ◽  
Kv4 Channels ◽  
Charged Residues ◽  
Arginine Residues ◽  
Voltage Sensing Domain ◽  
Positively Charged

The molecular and biophysical mechanisms by which voltage-sensitive K+ (Kv)4 channels inactivate and recover from inactivation are presently unresolved. There is a general consensus, however, that Shaker-like N- and P/C-type mechanisms are likely not involved. Kv4 channels also display prominent inactivation from preactivated closed states [closed-state inactivation (CSI)], a process that appears to be absent in Shaker channels. As in Shaker channels, voltage sensitivity in Kv4 channels is thought to be conferred by positively charged residues localized to the fourth transmembrane segment (S4) of the voltage-sensing domain. To investigate the role of S4 positive charge in Kv4.3 gating transitions, we analyzed the effects of charge elimination at each positively charged arginine (R) residue by mutation to the uncharged residue alanine (A). We first demonstrated that R290A, R293A, R296A, and R302A mutants each alter basic activation characteristics consistent with positive charge removal. We then found strong evidence that recovery from inactivation is coupled to deactivation, showed that the precise location of the arginine residues within S4 plays an important role in the degree of development of CSI and recovery from CSI, and demonstrated that the development of CSI can be sequentially uncoupled from activation by R296A, specifically. Taken together, these results extend our current understanding of Kv4.3 gating transitions.

scholarly journals Sec61p Contributes to Signal Sequence Orientation According to the Positive-Inside Rule

2004 ◽  
Vol 15 (3) ◽  
pp. 1470-1478 ◽  
Author(s):  
Veit Goder ◽  
Tina Junne ◽  
Martin Spiess
Keyword(s):  
Protein Targeting ◽  
Signal Sequence ◽  
Site Directed Mutagenesis ◽  
Diagnostic Model ◽  
Hydrophobic Core ◽  
Flanking Sequence ◽  
Charged Residues ◽  
Signal Anchor ◽  
A Charge

Protein targeting to the endoplasmic reticulum is mediated by signal or signal-anchor sequences. They also play an important role in protein topogenesis, because their orientation in the translocon determines whether their N- or C-terminal sequence is translocated. Signal orientation is primarily determined by charged residues flanking the hydrophobic core, whereby the more positive end is predominantly positioned to the cytoplasmic side of the membrane, a phenomenon known as the “positive-inside rule.” We tested the role of conserved charged residues of Sec61p, the major component of the translocon in Saccharomyces cerevisiae, in orienting signals according to their flanking charges by site-directed mutagenesis by using diagnostic model proteins. Mutation of R67, R74, or E382 in Sec61p reduced C-terminal translocation of a signal-anchor protein with a positive N-terminal flanking sequence and increased it for signal-anchor proteins with positive C-terminal sequences. These mutations produced a stronger effect on substrates with greater charge difference across the hydrophobic core of the signal. For some of the substrates, a charge mutation in Sec61p had a similar effect as one in the substrate polypeptides. Although these three residues do not account for the entire charge effect in signal orientation, the results show that Sec61p contributes to the positive-inside rule.

scholarly journals Role of Charged Residues in the S1-S4 Domains of Slo2.1 K+ Channels

2009 ◽  
Vol 96 (3) ◽  
pp. 482a
Author(s):  
Li Dai ◽  
Michael Sanguinetti
Keyword(s):  
K Channels ◽  
Charged Residues

Role of Positively Charged Residues Lys267, Lys270, and Arg411 of Cytochrome P450scc (Cyp11A1) in Interaction with Adrenodoxin

2005 ◽  
Vol 70 (6) ◽  
pp. 664-671 ◽  
Author(s):  
N. V. Strushkevich ◽  
T. N. Azeva ◽  
G. I. Lepesheva ◽  
S. A. Usanov
Keyword(s):  
Cytochrome P450scc ◽  
Charged Residues ◽  
Positively Charged

scholarly journals Critical Negatively Charged Residues Are Important for the Activity of SARS-CoV-1 and SARS-CoV-2 Fusion Peptides

2021 ◽  
Author(s):  
Alex L. Lai ◽  
Jack H. Freed
Keyword(s):  
Critical Role ◽  
Binding Energies ◽  
Host Cells ◽  
Topological Model ◽  
Pseudotyped Virus ◽  
Fusion Peptides ◽  
Human Pathogens ◽  
Charged Residues ◽  
The Difference

AbstractCoronaviruses are a major infectious disease threat, and include the human pathogens of zoonotic origin SARS-CoV (“SARS-1”), SARS-CoV-2 (“SARS-2”) and MERS-CoV (“MERS”). Entry of coronaviruses into host cells is mediated by the viral spike (S) protein. Previously, we identified that the domain immediately downstream of the S2’ cleavage site is the bona fide FP (amino acids 798-835) for SARS-1 using ESR spectroscopy technology. We also found that the SARS-1 FP induces membrane ordering in a Ca2+ dependent fashion. In this study, we want to know which residues are involved in this Ca2+ binding, to build a topological model and to understand the role of the Ca2+. We performed a systematic mutation study on the negatively charged residues on the SARS-1 FP. While all six negatively charged residues contributes to the membrane ordering activity of the FP to some extent, D812 is the most important residue. We provided a topological model of how the FP binds Ca2+ ions: both FP1 and FP2 bind one Ca2+ ion, and there are two binding sites in FP1 and three in FP2. We also found that the corresponding residue D830 in the SARS-2 FP plays a similar critical role. ITC experiments show that the binding energies between the FP and Ca2+ as well as between the FP and membranes also decreases for all mutants. The binding of Ca2+, the folding of FP and the ordering activity correlated very well across the mutants, suggesting that the function of the Ca2+ is to help to folding of FP in membranes to enhance its activity. Using a novel pseudotyped virus particle (PP)-liposome methodology, we monitored the membrane ordering induced by the FPs in the whole S proteins in its trimer form in real time. We found that the SARS-1 and SARS-2 PPs also induce membrane ordering as the separate FPs do, and the mutations of the negatively charged residues also greatly reduce the membrane ordering activity. However, the difference in kinetic between the PP and FP indicates a possible role of FP trimerization. This finding could lead to therapeutic solutions that either target the FP-calcium interaction or block the Ca2+ channel to combat the ongoing COVID-19 pandemic.

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