A novelDFNA9mutation in the vWFA2 domain ofCOCHalters a conserved cysteine residue and intrachain disulfide bond formation resulting in progressive hearing loss and site-specific vestibular and central oculomotor dysfunction

2005 ◽  
Vol 139A (2) ◽  
pp. 86-95 ◽  
Author(s):  
Valerie A. Street ◽  
Jeremy C. Kallman ◽  
Nahid G. Robertson ◽  
Sharon F. Kuo ◽  
Cynthia C. Morton ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Disulfide Bond ◽  
Bond Formation ◽  
Cysteine Residue ◽  
Disulfide Bond Formation ◽  
Progressive Hearing Loss ◽  
Site Specific ◽  
Intrachain Disulfide Bond

scholarly journals Formation and intracellular transport of a heterodimeric viral spike protein complex.

1991 ◽  
Vol 112 (2) ◽  
pp. 257-266 ◽  
Author(s):  
R Persson ◽  
R F Pettersson
Keyword(s):  
Disulfide Bond ◽  
Intracellular Transport ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Membrane Glycoproteins ◽  
Virus Particles ◽  
Viral Glycoproteins ◽  
Protein Disulfide ◽  
Kinetics Of ◽  
Intrachain Disulfide Bond

We have analyzed the heterodimerization and intracellular transport from the ER to the Golgi complex (GC) of two membrane glycoproteins of a bunyavirus (Uukuniemi virus) that matures by a budding process in the GC. The glycoproteins G1 and G2, which form the viral spikes, are cotranslationally cleaved in the ER from a 110,000-D precursor. Newly synthesized G1 was transported to the GC and incorporated into virus particles about 30-45 min faster than newly synthesized G2. Analysis of the kinetics of intrachain disulfide bond formation showed that G1 acquired its mature form within 10 min, while completion of disulfide bond formation of G2 required a considerably longer time (up to 60 min). During the maturation process, G2 was transiently associated with the IgG heavy chain binding protein for a longer time than G1. Protein disulfide isomerase also coprecipitated with antibodies against G1 and G2. In virus particles, G1 and G2 were present exclusively as heterodimers. Immunoprecipitation with monoclonal antibodies showed that heterodimerization occurred rapidly, probably in the ER, between newly made G1 and mature, dimerization competent G2. Taken together, our results show that these two viral glycoproteins have different maturation kinetics in the ER. We conclude that the apparent different kinetics of ER to GC transport of G1 and G2 is due to the different rates by which these proteins fold and become competent to enter into heterodimeric complexes prior to exit from the ER.

scholarly journals Functional Domain of Bovine Milk Lactoferrin Which Inhibits the Adherence of Streptococcus mutans Cells to a Salivary Film

2002 ◽  
Vol 70 (9) ◽  
pp. 5279-5282 ◽  
Author(s):  
Takahiko Oho ◽  
Morihide Mitoma ◽  
Toshihiko Koga
Keyword(s):  
Streptococcus Mutans ◽  
Disulfide Bond ◽  
Bond Formation ◽  
Bovine Milk ◽  
Cysteine Residue ◽  
Bovine Lactoferrin ◽  
Functional Domain ◽  
Disulfide Bond Formation ◽  
Serine Residue

ABSTRACT The bovine lactoferrin molecule and relatively long lactoferrin fragments containing residues 473 to 538 strongly inhibited adherence of Streptococcus mutans to saliva-coated hydroxyapatite beads. Each cysteine residue in Lf411 (residues 473 to 538) was replaced by a serine residue, and the mutants Lf411-C481S and Lf411-C532S strongly inhibited S. mutans adherence. These results suggest that the functional domain of lactoferrin that binds to a salivary film lies in residues 473 to 538 and that the region might be concealed by disulfide bond formation between Cys481 and Cys532 in the Lf411 fragment.

Two dileucine motifs mediate late endosomal/lysosomal targeting of transmembrane protein 192 (TMEM192) and a C-terminal cysteine residue is responsible for disulfide bond formation in TMEM192 homodimers

2011 ◽  
Vol 434 (2) ◽  
pp. 219-231 ◽  
Author(s):  
Jörg Behnke ◽  
Eeva-Liisa Eskelinen ◽  
Paul Saftig ◽  
Bernd Schröder
Keyword(s):  
Disulfide Bond ◽  
Disulfide Bonds ◽  
Transmembrane Protein ◽  
Bond Formation ◽  
Immunogold Labelling ◽  
Disulfide Bridge ◽  
Cysteine Residue ◽  
Disulfide Bond Formation ◽  
Transmembrane Segments ◽  
Late Endosomes

TMEM192 (transmembrane protein 192) is a novel constituent of late endosomal/lysosomal membranes with four potential transmembrane segments and an unknown function that was initially discovered by organellar proteomics. Subsequently, localization in late endosomes/lysosomes has been confirmed for overexpressed and endogenous TMEM192, and homodimers of TMEM192 linked by disulfide bonds have been reported. In the present study the molecular determinants of TMEM192 mediating its transport to late endosomes/lysosomes were analysed by using CD4 chimaeric constructs and mutagenesis of potential targeting motifs in TMEM192. Two directly adjacent N-terminally located dileucine motifs of the DXXLL-type were found to be critical for transport of TMEM192 to late endosomes/lysosomes. Whereas disruption of both dileucine motifs resulted in mistargeting of TMEM192 to the plasma membrane, each of the two motifs was sufficient to ensure correct targeting of TMEM192. In order to study disulfide bond formation, mutagenesis of cysteine residues was performed. Mutation of Cys266 abolished disulfide bridge formation between TMEM192 molecules, indicating that TMEM192 dimers are linked by a disulfide bridge between their C-terminal tails. According to the predicted topology, Cys266 would be localized in the reductive milieu of the cytosol where disulfide bridges are generally uncommon. Using immunogold labelling and proteinase protection assays, the localization of the N- and C-termini of TMEM192 on the cytosolic side of the late endosomal/lysosomal membrane was experimentally confirmed. These findings may imply close proximity of the C-termini in TMEM192 dimers and a possible involvement of this part of the protein in dimer assembly.

scholarly journals Conversion of Bacillus subtilis OhrR from a 1-Cys to a 2-Cys Peroxide Sensor

2008 ◽  
Vol 190 (17) ◽  
pp. 5738-5745 ◽  
Author(s):  
Sumarin Soonsanga ◽  
Jin-Won Lee ◽  
John D. Helmann
Keyword(s):  
Molecular Weight ◽  
Bacillus Subtilis ◽  
Disulfide Bond ◽  
Active Sites ◽  
Xanthomonas Campestris ◽  
Bond Formation ◽  
Cysteine Residue ◽  
Low Molecular Weight ◽  
Disulfide Bond Formation ◽  
Protein Dimer

ABSTRACTOhrR proteins can be divided into two groups based on their inactivation mechanism: 1-Cys (represented byBacillus subtilisOhrR) and 2-Cys (represented byXanthomonas campestrisOhrR). A conserved cysteine residue near the amino terminus is present in both groups of proteins and is initially oxidized to the sulfenic acid. TheB. subtilis1-Cys OhrR protein is subsequently inactivated by formation of a mixed-disulfide bond with low-molecular-weight thiols or by cysteine overoxidation to sulfinic and sulfonic acids. In contrast, theX. campestris2-Cys OhrR is inactivated when the initially oxidized cysteine sulfenate forms an intersubunit disulfide bond with a second Cys residue from the other subunit of the protein dimer. Here, we demonstrate that the 1-CysB. subtilisOhrR can be converted into a 2-Cys OhrR by introducing another cysteine residue in either position 120 or position 124. Like theX. campestrisOhrR protein, these mutants (G120C and Q124C) are inactivated by intermolecular disulfide bond formation. Analysis of oxidized 2-Cys variants both in vivo and in vitro indicates that intersubunit disulfide bond formation can occur simultaneously at both active sites in the protein dimer. Rapid formation of intersubunit disulfide bonds protects OhrR against irreversible overoxidation in the presence of strong oxidants much more efficiently than do the endogenous low-molecular-weight thiols.

scholarly journals Oxygen-independent disulfide bond formation in VEGF-A and CA9

2021 ◽  
pp. 100505
Author(s):  
Fiana Levitin ◽  
Sandy Che-Eun Serena Lee ◽  
Stephanie Hulme ◽  
Ryan A. Rumantir ◽  
Amy S. Wong ◽  
...  
Keyword(s):  
Disulfide Bond ◽  
Bond Formation ◽  
Disulfide Bond Formation
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