Structural comparison of highly similar nucleoside-diphosphate kinases: Molecular explanation of distinct membrane-binding behavior

Biochimie ◽  
2014 ◽  
Vol 105 ◽  
pp. 110-118 ◽  
Author(s):  
L. Francois-Moutal ◽  
O. Marcillat ◽  
T. Granjon
Keyword(s):  
Membrane Binding ◽  
Structural Comparison ◽  
Binding Behavior ◽  
Nucleoside Diphosphate Kinases ◽  
Distinct Membrane

scholarly journals Structural Basis for the Distinct Membrane Binding Activity of the Homologous C2A Domains of Myoferlin and Dysferlin

2019 ◽  
Vol 431 (11) ◽  
pp. 2112-2126 ◽  
Author(s):  
Faraz M. Harsini ◽  
Anthony A. Bui ◽  
Anne M. Rice ◽  
Sukanya Chebrolu ◽  
Kerry L. Fuson ◽  
...  
Keyword(s):  
Membrane Binding ◽  
Binding Activity ◽  
Structural Basis ◽  
Distinct Membrane

scholarly journals Electrostatically Driven Encapsulation of Hydrophilic, Non-Conformational Peptide Epitopes into Liposomes

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 619 ◽  
Author(s):  
Ehsan Suleiman ◽  
Dominik Damm ◽  
Mirjam Batzoni ◽  
Vladimir Temchura ◽  
Andreas Wagner ◽  
...  
Keyword(s):  
Lipid Membranes ◽  
Membrane Binding ◽  
Terminal Sequence ◽  
Relevant Issue ◽  
Wide Audience ◽  
Microfluidic Mixing ◽  
Systematic Screening ◽  
Peptide Epitopes ◽  
Binding Behavior

Since the first use of liposomes as carriers for antigens, much work has been done to elucidate the mechanisms involved in the encapsulation of vaccine-relevant biomolecules. However, only a few studies have specifically investigated the encapsulation of hydrophilic, non-conformational peptide epitopes. We performed comprehensive and systematic screening studies, in order to identify conditions that favor the electrostatic interaction of such peptides with lipid membranes. Moreover, we have explored bi-terminal sequence extension as an approach to modify the isoelectric point of peptides, in order to modulate their membrane binding behavior and eventually shift/expand the working range under which they can be efficiently encapsulated in an electrostatically driven manner. The findings of our membrane interaction studies were then applied to preparing peptide-loaded liposomes. Our results show that the magnitude of membrane binding observed in our exploratory in situ setup translates to corresponding levels of encapsulation efficiency in both of the two most commonly employed methods for the preparation of liposomes, i.e., thin-film hydration and microfluidic mixing. We believe that the methods and findings described in the present studies will be of use to a wide audience and can be applied to address the ongoing relevant issue of the efficient encapsulation of hydrophilic biomolecules.

Annexins – insights from knockout mice

2016 ◽  
Vol 397 (10) ◽  
pp. 1031-1053 ◽  
Author(s):  
Thomas Grewal ◽  
Sundeep J. Wason ◽  
Carlos Enrich ◽  
Carles Rentero
Keyword(s):  
Mouse Models ◽  
Membrane Trafficking ◽  
Membrane Binding ◽  
Dependent Manner ◽  
Binding Characteristics ◽  
Binding Behavior ◽  
Interaction Partners ◽  
Health And Disease ◽  
Underlying Mechanisms

AbstractAnnexins are a highly conserved protein family that bind to phospholipids in a calcium (Ca2+) – dependent manner. Studies with purified annexins, as well as overexpression and knockdown approaches identified multiple functions predominantly linked to their dynamic and reversible membrane binding behavior. However, most annexins are found at multiple locations and interact with numerous proteins. Furthermore, similar membrane binding characteristics, overlapping localizations and shared interaction partners have complicated identification of their precise functions. To gain insight into annexin functionin vivo, mouse models deficient of annexin A1 (AnxA1), A2, A4, A5, A6 and A7 have been generated. Interestingly, with the exception of one study, all mice strains lacking one or even two annexins are viable and develop normally. This suggested redundancy within annexins, but examining these knockout (KO) strains under stress conditions revealed striking phenotypes, identifying underlying mechanisms specific for individual annexins, often supporting Ca2+homeostasis and membrane transport as central for annexin biology. Conversely, mice lacking AnxA1 or A2 show extracellular functions relevant in health and disease that appear independent of membrane trafficking or Ca2+signaling. This review will summarize the mechanistic insights gained from studies utilizing mouse models lacking members of the annexin family.

scholarly journals Structural comparison of the Caenorhabditis elegans and human Ndc80 complexes bound to microtubules reveals distinct binding behavior

2016 ◽  
Vol 27 (8) ◽  
pp. 1197-1203 ◽  
Author(s):  
Elizabeth M. Wilson-Kubalek ◽  
Iain M. Cheeseman ◽  
Ronald A. Milligan
Keyword(s):  
Caenorhabditis Elegans ◽  
Molecular Basis ◽  
Structural Comparison ◽  
Direct Role ◽  
C Elegans ◽  
Binding Behavior ◽  
Cryo Electron Microscopy ◽  
Ndc80 Complex ◽  
Structural Differences ◽  
Dynamic Microtubule

During cell division, kinetochores must remain tethered to the plus ends of dynamic microtubule polymers. However, the molecular basis for robust kinetochore–microtubule interactions remains poorly understood. The conserved four-subunit Ndc80 complex plays an essential and direct role in generating dynamic kinetochore–microtubule attachments. Here we compare the binding of the Caenorhabditis elegans and human Ndc80 complexes to microtubules at high resolution using cryo–electron microscopy reconstructions. Despite the conserved roles of the Ndc80 complex in diverse organisms, we find that the attachment mode of these complexes for microtubules is distinct. The human Ndc80 complex binds every tubulin monomer along the microtubule protofilament, whereas the C. elegans Ndc80 complex binds more tightly to β-tubulin. In addition, the C. elegans Ndc80 complex tilts more toward the adjacent protofilament. These structural differences in the Ndc80 complex between different species may play significant roles in the nature of kinetochore–microtubule interactions.

scholarly journals Conservative mutations in the C2 domains of factor VIII and factor V alter phospholipid binding and cofactor activity

Blood ◽  
2012 ◽  
Vol 120 (9) ◽  
pp. 1923-1932 ◽  
Author(s):  
Gary E. Gilbert ◽  
Valerie A. Novakovic ◽  
Randal J. Kaufman ◽  
Hongzhi Miao ◽  
Steven W. Pipe
Keyword(s):  
Amino Acids ◽  
Factor Viii ◽  
Membrane Binding ◽  
Fold Increase ◽  
Factor V ◽  
Factor X ◽  
C2 Domains ◽  
Hydrophobic Amino Acids ◽  
Increased Activity ◽  
Distinct Membrane

Abstract Factor VIII and factor V share structural homology and bind to phospholipid membranes via tandem, lectin-like C domains. Their respective C2 domains bind via 2 pairs of hydrophobic amino acids and an amphipathic cluster. In contrast, the factor V-like, homologous subunit (Pt-FV) of a prothrombin activator from Pseudonaja textilis venom is reported to function without membrane binding. We hypothesized that the distinct membrane-interactive amino acids of these proteins contribute to the differing membrane-dependent properties. We prepared mutants in which the C2 domain hydrophobic amino acid pairs were changed to the homologous residues of the other protein and a factor V mutant with 5 amino acids changed to those from Pt-FV (FVMTTS/Y). Factor VIII mutants were active on additional membrane sites and had altered apparent affinities for factor X. Some factor V mutants, including FVMTTS/Y, had increased membrane interaction and apparent membrane-independent activity that was the result of phospholipid retained during purification. Phospholipid-free FVMTTS/Y showed increased activity, particularly a 10-fold increase in activity on membranes lacking phosphatidylserine. The reduced phosphatidylserine requirement correlated to increased activity on resting and stimulated platelets. We hypothesize that altered membrane binding contributes to toxicity of Pt-FV.

Sign in / Sign up

Export Citation Format

Share Document