scholarly journals Sequestosome 1 Is Part of the Interaction Network of VAPB

2021 ◽  
Vol 22 (24) ◽  
pp. 13271
Author(s):  
Christina James ◽  
Christof Lenz ◽  
Henning Urlaub ◽  
Ralph H. Kehlenbach
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Protein ◽  
Protein Interactions ◽  
Single Point ◽  
Interaction Network ◽  
Single Point Mutation ◽  
Sequestosome 1 ◽  
Binding Partners ◽  
Multiple Protein ◽  
Familial Form

VAPB (Vesicle-Associated-membrane Protein-associated protein B) is a tail-anchored membrane protein of the endoplasmic reticulum that can also be detected at the inner nuclear membrane. As a component of many contact sites between the endoplasmic reticulum and other organelles, VAPB is engaged in multiple protein interactions with a plethora of binding partners. A mutant version of VAPB, P56S-VAPB, which results from a single point mutation, is involved in a familial form of amyotrophic lateral sclerosis (ALS8). We performed RAPIDS (rapamycin- and APEX-dependent identification of proteins by SILAC) to identify proteins that interact with or are in close proximity to P56S-VAPB. The mutation abrogates the interaction of VAPB with many known binding partners. Here, we identify Sequestosome 1 (SQSTM1), a well-known autophagic adapter protein, as a major interaction/proximity partner of P56S-VAPB. Remarkably, not only the mutant protein, but also wild-type VAPB interacts with SQSTM1, as shown by proximity ligation assays and co-immunoprecipiation experiments.

scholarly journals The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9 is crucial for TLR signaling

2007 ◽  
Vol 177 (2) ◽  
pp. 265-275 ◽  
Author(s):  
Melanie M. Brinkmann ◽  
Eric Spooner ◽  
Kasper Hoebe ◽  
Bruce Beutler ◽  
Hidde L. Ploegh ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Bone Marrow ◽  
Membrane Protein ◽  
Point Mutation ◽  
Single Point ◽  
Single Point Mutation ◽  
Physical Interaction ◽  
Tlr Signaling ◽  
Viral Pathogens ◽  
Transduction Mechanisms

Toll-like receptors (TLRs) sense the presence of microbial and viral pathogens by signal transduction mechanisms that remain to be fully elucidated. A single point mutation (H412R) in the polytopic endoplasmic reticulum (ER)–resident membrane protein UNC93B abolishes signaling via TLR3, 7, and 9. We show that UNC93B specifically interacts with TLR3, 7, 9, and 13, whereas introduction of the point mutation H412R in UNC93B abolishes their interactions. We establish the physical interaction of the intracellular TLRs with UNC93B in splenocytes and bone marrow–derived dendritic cells. Further, by expressing chimeric TLRs, we show that TLR3 and 9 bind to UNC93B via their transmembrane domains. We propose that a physical association between UNC93B and TLRs in the ER is essential for proper TLR signaling.

scholarly journals Analyzing Effects of Naturally Occurring Missense Mutations

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Zhe Zhang ◽  
Maria A. Miteva ◽  
Lin Wang ◽  
Emil Alexov
Keyword(s):  
Amino Acid ◽  
Protein Stability ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Single Point ◽  
3D Structure ◽  
Genetic Mutation ◽  
Single Point Mutation ◽  
Missense Mutations ◽  
Single Nucleotide

Single-point mutation in genome, for example, single-nucleotide polymorphism (SNP) or rare genetic mutation, is the change of a single nucleotide for another in the genome sequence. Some of them will produce an amino acid substitution in the corresponding protein sequence (missense mutations); others will not. This paper focuses on genetic mutations resulting in a change in the amino acid sequence of the corresponding protein and how to assess their effects on protein wild-type characteristics. The existing methods and approaches for predicting the effects of mutation on protein stability, structure, and dynamics are outlined and discussed with respect to their underlying principles. Available resources, either as stand-alone applications or webservers, are pointed out as well. It is emphasized that understanding the molecular mechanisms behind these effects due to these missense mutations is of critical importance for detecting disease-causing mutations. The paper provides several examples of the application of 3D structure-based methods to model the effects of protein stability and protein-protein interactions caused by missense mutations as well.

TMCC3 localizes at the three-way junctions for the proper tubular network of the endoplasmic reticulum

2019 ◽  
Vol 476 (21) ◽  
pp. 3241-3260
Author(s):  
Sindhu Wisesa ◽  
Yasunori Yamamoto ◽  
Toshiaki Sakisaka
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Proteins ◽  
Membrane Protein ◽  
Mammalian Cells ◽  
Coiled Coil ◽  
Transmembrane Domains ◽  
Domain Family ◽  
Coiled Coil Domain ◽  
U2os Cells ◽  
Er Membrane

The tubular network of the endoplasmic reticulum (ER) is formed by connecting ER tubules through three-way junctions. Two classes of the conserved ER membrane proteins, atlastins and lunapark, have been shown to reside at the three-way junctions so far and be involved in the generation and stabilization of the three-way junctions. In this study, we report TMCC3 (transmembrane and coiled-coil domain family 3), a member of the TEX28 family, as another ER membrane protein that resides at the three-way junctions in mammalian cells. When the TEX28 family members were transfected into U2OS cells, TMCC3 specifically localized at the three-way junctions in the peripheral ER. TMCC3 bound to atlastins through the C-terminal transmembrane domains. A TMCC3 mutant lacking the N-terminal coiled-coil domain abolished localization to the three-way junctions, suggesting that TMCC3 localized independently of binding to atlastins. TMCC3 knockdown caused a decrease in the number of three-way junctions and expansion of ER sheets, leading to a reduction of the tubular ER network in U2OS cells. The TMCC3 knockdown phenotype was partially rescued by the overexpression of atlastin-2, suggesting that TMCC3 knockdown would decrease the activity of atlastins. These results indicate that TMCC3 localizes at the three-way junctions for the proper tubular ER network.

Sign in / Sign up

Export Citation Format

Share Document