Shifting Polar Residues Across Primary Sequence Frames of Transmembrane Domains Calibrates Membrane Permeation Thermodynamics

Biochemistry ◽  
2020 ◽  
Vol 59 (45) ◽  
pp. 4353-4366
Author(s):  
Souvik Sinha ◽  
Shubhra Ghosh Dastidar
Keyword(s):  
Transmembrane Domains ◽  
Membrane Permeation ◽  
Primary Sequence ◽  
Polar Residues

scholarly journals The Cytoplasmic End of Transmembrane Domain 3 Regulates the Activity of the Saccharomyces cerevisiae G-Protein-Coupled α-Factor Receptor

Genetics ◽  
2002 ◽  
Vol 160 (2) ◽  
pp. 429-443
Author(s):  
William Parrish ◽  
Markus Eilers ◽  
Weiwen Ying ◽  
James B Konopka
Keyword(s):  
G Protein ◽  
Transmembrane Domain ◽  
Transmembrane Helix ◽  
G Protein Coupled Receptors ◽  
Transmembrane Domains ◽  
Targeted Mutagenesis ◽  
Activating Mutations ◽  
Polar Residues ◽  
Domain 3 ◽  
G Protein Coupled

Abstract The binding of α-factor to its receptor (Ste2p) activates a G-protein-signaling pathway leading to conjugation of MATa cells of the budding yeast S. cerevisiae. We conducted a genetic screen to identify constitutively activating mutations in the N-terminal region of the α-factor receptor that includes transmembrane domains 1–5. This approach identified 12 unique constitutively activating mutations, the strongest of which affected polar residues at the cytoplasmic ends of transmembrane domains 2 and 3 (Asn84 and Gln149, respectively) that are conserved in the α-factor receptors of divergent yeast species. Targeted mutagenesis, in combination with molecular modeling studies, suggested that Gln149 is oriented toward the core of the transmembrane helix bundle where it may be involved in mediating an interaction with Asn84. These residues appear to play specific roles in maintaining the inactive conformation of the protein since a variety of mutations at either position cause constitutive receptor signaling. Interestingly, the activity of many mammalian G-protein-coupled receptors is also regulated by conserved polar residues (the E/DRY motif) at the cytoplasmic end of transmembrane domain 3. Altogether, the results of this study suggest a conserved role for the cytoplasmic end of transmembrane domain 3 in regulating the activity of divergent G-protein-coupled receptors.

scholarly journals Polar Residues in the Transmembrane Domains of the Type 1 Angiotensin II Receptor Are Required for Binding and Coupling

1996 ◽  
Vol 271 (3) ◽  
pp. 1507-1513 ◽  
Author(s):  
Catherine Monnot ◽  
Claire Bihoreau ◽  
Sophie Conchon ◽  
Kathleen M. Curnow ◽  
Pierre Corvol ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Transmembrane Domains ◽  
Angiotensin Ii Receptor ◽  
Polar Residues

scholarly journals ABCG subfamily (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Ian Kerr
Keyword(s):  
Nucleotide Binding ◽  
Binding Domain ◽  
Transmembrane Domains ◽  
Primary Sequence ◽  
Nucleotide Binding Domain ◽  
Transporter Structure

This family of 'half-transporters' act as homo- or heterodimers; particularly ABCG5 and ABCG8 are thought to be obligate heterodimers. The ABCG5/ABCG heterodimer sterol transporter structure has been determined [4], suggesting an extensive intracellular nucleotide binding domain linked to the transmembrane domains by a fold in the primary sequence. The functional ABCG2 transporter appears to be a homodimer with structural similarities to the ABCG5/ABCG8 heterodimer [7].

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.

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