scholarly journals Cryo-EM structures of human TMEM120A and TMEM120B

2021 ◽  
Author(s):  
Meng Ke ◽  
Yue Yu ◽  
Changjian Zhao ◽  
Shirong Lai ◽  
Qiang Su ◽  
...  
Keyword(s):  
Potential Role ◽  
Transmembrane Domain ◽  
Transmembrane Protein ◽  
Expression System ◽  
Coiled Coil ◽  
Fatty Acid Elongase ◽  
Coiled Coil Domain ◽  
Induced Currents ◽  
The Difference

TMEM120A (Transmembrane protein 120A) was recently identified as a mechanical pain sensing ion channel named as TACAN, while its homologue TMEM120B has no mechanosensing property1. Here, we report the cryo-EM structures of both human TMEM120A and TMEM120B. The two structures share the same dimeric assembly, mediated by extensive interactions through the transmembrane domain (TMD) and the N-terminal coiled coil domain (CCD). However, the nearly identical structures cannot provide clues for the difference in mechanosensing between TMEM120A and TMEM120B. Although TMEM120A could mediate conducting currents in a bilayer system, it does not mediate mechanical-induced currents in a heterologous expression system, suggesting TMEM120A is unlikely a mechanosensing channel. Instead, the TMDs of TMEM120A and TMEM120B resemble the structure of a fatty acid elongase, ELOVL7, indicating their potential role of an enzyme in lipid metabolism.

scholarly journals Structure of an atypical FeoB G-domain reveals a putative domain-swapped dimer

2013 ◽  
Vol 69 (4) ◽  
pp. 399-404 ◽  
Author(s):  
Chandrika N. Deshpande ◽  
Aaron P. McGrath ◽  
Josep Font ◽  
Amy P. Guilfoyle ◽  
Megan J. Maher ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Ferrous Iron ◽  
Iron Uptake ◽  
Transmembrane Domain ◽  
Transmembrane Protein ◽  
Gtpase Domain ◽  
Helical Domain ◽  
Precise Role ◽  
Putative Domain

FeoB is a transmembrane protein involved in ferrous iron uptake in prokaryotic organisms. FeoB comprises a cytoplasmic soluble domain termed NFeoB and a C-terminal polytopic transmembrane domain. Recent structures of NFeoB have revealed two structural subdomains: a canonical GTPase domain and a five-helix helical domain. The GTPase domain hydrolyses GTP to GDP through a well characterized mechanism, a process which is required for Fe2+transport. In contrast, the precise role of the helical domain has not yet been fully determined. Here, the structure of the cytoplasmic domain of FeoB fromGallionella capsiferriformansis reported. Unlike recent structures of NFeoB, theG. capsiferriformansNFeoB structure is highly unusual in that it does not contain a helical domain. The crystal structures of both apo and GDP-bound protein forms a domain-swapped dimer.

scholarly journals Lumenal Endosomal and Golgi-Retrieval Determinants Involved in pH-sensitive Targeting of an Early Golgi Protein

2001 ◽  
Vol 12 (10) ◽  
pp. 3152-3160 ◽  
Author(s):  
Collin Bachert ◽  
Tina H. Lee ◽  
Adam D. Linstedt
Keyword(s):  
Transmembrane Domain ◽  
Coiled Coil ◽  
Ph Sensitive ◽  
Plasma Membrane Protein ◽  
Golgi Transport ◽  
Coiled Coil Domain ◽  
Golgi Localization ◽  
Golgi Protein ◽  
Lumenal Domain ◽  
Chimeric Molecules

Despite the potential importance of retrieval-based targeting, few Golgi cisternae-localized proteins have been demonstrated to be targeted by retrieval, and the putative retrieval signals remain unknown. Golgi phosphoprotein of 130 kDa (GPP130) is acis-Golgi protein that allows assay of retrieval-based targeting because it redistributes to endosomes upon treatment with agents that disrupt lumenal pH, and it undergoes endosome-to-Golgi retrieval upon drug removal. Analysis of chimeric molecules containing domains from GPP130 and the plasma membrane protein dipeptidylpeptidase IV indicated that GPP130 targeting information is contained entirely within its lumenal domain. Dissection of the lumenal domain indicated that a predicted coiled-coil stem domain adjacent to the transmembrane domain was both required and sufficient for pH-sensitive Golgi localization and endosome-to-Golgi retrieval. Further dissection of this stem domain revealed two noncontiguous stretches that each conferred Golgi localization separated by a stretch that conferred endosomal targeting. Importantly, in the absence of the endosomal determinant the Golgi targeting of constructs containing either or both of the Golgi determinants became insensitive to pH disruption by monensin. Because monensin blocks endosome-to-Golgi transport, the finding that the endosomal determinant confers monensin sensitivity suggests that the endosomal determinant causes GPP130 to traffic to endosomes from which it is normally retrieved. Thus, our observations identify Golgi and endosomal targeting determinants within a lumenal predicted coiled-coil domain that appear to act coordinately to mediate retrieval-based targeting of GPP130.

scholarly journals Mutations in the Drosophila hook gene inhibit endocytosis of the boss transmembrane ligand into multivesicular bodies.

1996 ◽  
Vol 133 (6) ◽  
pp. 1205-1215 ◽  
Author(s):  
H Krämer ◽  
M Phistry
Keyword(s):  
Amino Acids ◽  
Transmembrane Protein ◽  
Coiled Coil ◽  
Specific Pattern ◽  
Multivesicular Bodies ◽  
Endocytic Compartment ◽  
Coiled Coil Domain ◽  
Type Pattern ◽  
Cell Type Specific ◽  
Endocytic Vesicles

Transmembrane ligands can be internalized across cell boundaries into receptor-expressing cells. In the developing Drosophila eye imaginal disc, the bride of sevenless transmembrane protein (boss) is expressed on the surface of R8 cells. After internalization into neighboring R7 cells, the boss protein accumulates in multivesicular bodies. In a search for genes that affect this cell-type-specific pattern of boss endocytosis, we found that mutations in the hook gene inhibit the accumulation of boss in multivesicular bodies of R7 cells. In addition, hook flies exhibit pleiotropic phenotypes including abnormal bristle morphology and eye degeneration. The wild-type-pattern of boss endocytosis was restored in hook mutants by a genomic rescue fragment containing the hook gene or by a hook cDNA expressed in R7 cells under control of a sevenless (sev) enhancer. The hook gene encodes a novel cytoplasmic protein of 679 amino acids with a central coiled-coil domain of some 200 amino acids. Truncated, epitope-tagged hook proteins coimmunoprecipitated the full-length protein, indicating dimerization mediated by the coiled-coil domain. The hook protein localizes to vesicular structures that are part of the endocytic compartment. The requirement of the hook protein in R7 cells for the accumulation of boss protein in multivesicular bodies, and the localization of the hook protein to endocytic vesicles indicate that the hook gene encodes a novel component of the endocytic compartment that plays an important role in the endocytosis of transmembrane ligands or their transport to multivesicular bodies.

scholarly journals Role of the TFG N-terminus and coiled-coil domain in the transforming activity of the thyroid TRK-T3 oncogene

Oncogene ◽  
1998 ◽  
Vol 16 (6) ◽  
pp. 809-816 ◽  
Author(s):  
Angela Greco ◽  
Lisa Fusetti ◽  
Claudia Miranda ◽  
Riccardo Villa ◽  
Simona Zanotti ◽  
...  
Keyword(s):  
Coiled Coil ◽  
Coiled Coil Domain ◽  
N Terminus ◽  
Transforming Activity

scholarly journals TMCO1expression Promotes Cell Proliferation and Induces Epithelial-mesenchymal Transformation in Human Gliomas

2021 ◽  
Author(s):  
lun gao ◽  
Zhang Ye ◽  
Jun-Hui Liu ◽  
Ji-An Yang ◽  
Yong Li ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Transmembrane Protein ◽  
Critical Role ◽  
Coiled Coil ◽  
World Health ◽  
Migration And Invasion ◽  
Who Grade ◽  
Mesenchymal Transition ◽  
Mesenchymal Transformation

Abstract Transmembrane and coiled-coil domains 1 (TMCO1) is a recently discovered transmembrane protein of endoplasmic reticulum (ER), which plays a critical role in maintaining calcium homeostasis. TMCO1 dysfunction has been proved to be closely related to a variety of human diseases, including glaucoma, deformities, mental retardation and tumorigenesis. However, the role of TMCO1 in gliomas remains unclear. The purpose of this study was to detect the role of TMCO1 in the pathogenesis and progression of gliomas. This study demonstrated that TMCO1 was up-regulated in gliomas and its overexpression predicted poor prognosis. We also revealed that the expression of TMCO1 was associated with the World Health Organization (WHO) grade of gliomas. Knockdown of TMCO1 inhibited the proliferation and induced apoptosis of U87 and U251cells. In addition, TMCO1 induced GBM cell migration and invasion by promoting epithelial-mesenchymal transition (EMT). These dates collectively proved the crucial role of TMCO1 as a novel prognostic factor and underlying therapeutic target for glioma patients.

Fracture of SnBi/Ni(P) interfaces

2005 ◽  
Vol 20 (4) ◽  
pp. 818-826 ◽  
Author(s):  
P.L. Liu ◽  
J.K. Shang
Keyword(s):  
Fracture Mechanism ◽  
Fracture Resistance ◽  
Potential Role ◽  
Substrate Interface ◽  
Interfacial Segregation ◽  
The Difference ◽  
Cu Interconnect ◽  
Electroless Ni ◽  
Bi Segregation

Fracture resistance of the interface between electroless Ni(P) and the eutectic SnBi solder alloy was examined in the as-reflowed and aged conditions, to investigate the potential role of Ni in inhibiting interfacial segregation of Bi in SnBi–Cu interconnect. In the as-reflowed condition, the fracture resistance of the SnBi/Ni(P) interface was about the same as that of the SnBi/Cu interface. Upon aging at 120 °C for 7 days the fracture resistance of the SnBi/Ni(P) interface was much higher than that of the SnBi/Cu interface. Such a difference was shown to result from the difference in fracture mechanism as the crack remained along the solder–intermetallic interface in the aged SnBi–Ni interconnect but propagated along the intermetallic–substrate interface in the aged SnBi–Cu interconnect. While fracture of the intermetallic–substrate interface in SnBi–Cu interconnect was due to Bi segregation onto that interface, no Bi was detected at the intermetallic-substrate interface in SnBi–Ni interconnects, implying that Ni(P) was effective in inhibiting the interfacial segregation of Bi.

scholarly journals Role of TFG sequences outside the coiled-coil domain in TRK-T3 oncogenic activation

Oncogene ◽  
2003 ◽  
Vol 22 (6) ◽  
pp. 807-818 ◽  
Author(s):  
Emanuela Roccato ◽  
Sonia Pagliardini ◽  
Loredana Cleris ◽  
Silvana Canevari ◽  
Franca Formelli ◽  
...  
Keyword(s):  
Coiled Coil ◽  
Coiled Coil Domain

scholarly journals Dimerization of the ATRIP Protein through the Coiled-Coil Motif and Its Implication to the Maintenance of Stalled Replication Forks

2005 ◽  
Vol 16 (12) ◽  
pp. 5551-5562 ◽  
Author(s):  
Eisuke Itakura ◽  
Isao Sawada ◽  
Akira Matsuura
Keyword(s):  
Mammalian Cells ◽  
Coiled Coil ◽  
Genotoxic Stress ◽  
Replication Forks ◽  
Cycle Arrest ◽  
Coiled Coil Domain ◽  
Functional Complex ◽  
Stalled Replication Forks

ATR (ATM and Rad3-related), a PI kinase-related kinase (PIKK), has been implicated in the DNA structure checkpoint in mammalian cells. ATR associates with its partner protein ATRIP to form a functional complex in the nucleus. In this study, we investigated the role of the ATRIP coiled-coil domain in ATR-mediated processes. The coiled-coil domain of human ATRIP contributes to self-dimerization in vivo, which is important for the stable translocation of the ATR-ATRIP complex to nuclear foci that are formed after exposure to genotoxic stress. The expression of dimerization-defective ATRIP diminishes the maintenance of replication forks during treatment with replication inhibitors. By contrast, it does not compromise the G2/M checkpoint after IR-induced DNA damage. These results show that there are two critical functions of ATR-ATRIP after the exposure to genotoxic stress: maintenance of the integrity of replication machinery and execution of cell cycle arrest, which are separable and are achieved via distinct mechanisms. The former function may involve the concentrated localization of ATR to damaged sites for which the ATRIP coiled-coil motif is critical.

scholarly journals Proprotein cleavage of E-cadherin by furin in baculovirus over-expression system: potential role of other convertases in mammalian cells

FEBS Letters ◽  
1998 ◽  
Vol 438 (3) ◽  
pp. 306-310 ◽  
Author(s):  
Horst Posthaus ◽  
Claire M. Dubois ◽  
Marie-Hélène Laprise ◽  
Francine Grondin ◽  
Maja M. Suter ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Potential Role ◽  
Expression System ◽  
Over Expression ◽  
E Cadherin

scholarly journals TMEM120A contains a specific coenzyme A-binding site and might not mediate poking- or stretch-induced channel activities in cells

2021 ◽  
Author(s):  
Yao Rong ◽  
Jinghui Jiang ◽  
Yiwei Gao ◽  
Jianli Guo ◽  
Danfeng Song ◽  
...  
Keyword(s):  
Coenzyme A ◽  
Transmembrane Domain ◽  
Transmembrane Protein ◽  
Coiled Coil ◽  
Tryptophan Residue ◽  
Amino Acid Residues ◽  
Functional Roles ◽  
Amino Terminal ◽  
Membrane Spanning ◽  
In Cells

TMEM120A, a member of the Transmembrane protein 120 (TMEM120) family, has pivotal function in adipocyte differentiation and metabolism, and may also contribute to sensing mechanical pain by functioning as an ion channel named TACAN. Here we report that expression of TMEM120A is not sufficient in mediating poking- or stretch-induced currents in cells, and have solved cryo-EM structures of human TMEM120A (HsTMEM120A) in complex with an endogenous metabolic cofactor (coenzyme A, CoASH) and in the apo form. HsTMEM120A forms a symmetrical homodimer with each monomer containing an amino-terminal coiled-coil motif followed by a transmembrane domain with six membrane-spanning helices. Within the transmembrane domain, a CoASH molecule is hosted in a deep cavity and forms specific interactions with nearby amino acid residues. Mutation of a central tryptophan residue involved in binding CoASH dramatically reduced the binding affinity of HsTMEM120A with CoASH. HsTMEM120A exhibits distinct conformations at the states with or without CoASH bound. Our results suggest that TMEM120A may have alternative functional roles potentially involved in CoASH transport, sensing or metabolism.

Sign in / Sign up

Export Citation Format

Share Document