scholarly journals Author response: Global alignment and assessment of TRP channel transmembrane domain structures to explore functional mechanisms

2020 ◽  
Author(s):  
Katherine E Huffer ◽  
Antoniya A Aleksandrova ◽  
Andrés Jara-Oseguera ◽  
Lucy R Forrest ◽  
Kenton J Swartz
Keyword(s):  
Transmembrane Domain ◽  
Trp Channel ◽  
Author Response ◽  
Global Alignment ◽  
Domain Structures ◽  
Functional Mechanisms

scholarly journals Global alignment and assessment of TRP channel transmembrane domain structures to explore functional mechanisms

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Katherine E Huffer ◽  
Antoniya A Aleksandrova ◽  
Andrés Jara-Oseguera ◽  
Lucy R Forrest ◽  
Kenton J Swartz
Keyword(s):  
Transmembrane Domain ◽  
Ion Selectivity ◽  
Structural Data ◽  
Trp Channel ◽  
Structural Basis ◽  
Global Alignment ◽  
Functional Studies ◽  
Domain Structures ◽  
Mechanistic Basis ◽  
Channel Structures

The recent proliferation of published TRP channel structures provides a foundation for understanding the diverse functional properties of this important family of ion channel proteins. To facilitate mechanistic investigations, we constructed a structure-based alignment of the transmembrane domains of 120 TRP channel structures. Comparison of structures determined in the absence or presence of activating stimuli reveals similar constrictions in the central ion permeation pathway near the intracellular end of the S6 helices, pointing to a conserved cytoplasmic gate and suggesting that most available structures represent non-conducting states. Comparison of the ion selectivity filters toward the extracellular end of the pore supports existing hypotheses for mechanisms of ion selectivity. Also conserved to varying extents are hot spots for interactions with hydrophobic ligands, lipids and ions, as well as discrete alterations in helix conformations. This analysis therefore provides a framework for investigating the structural basis of TRP channel gating mechanisms and pharmacology, and, despite the large number of structures included, reveals the need for additional structural data and for more functional studies to establish the mechanistic basis of TRP channel function.

scholarly journals Global alignment and assessment of TRP channel transmembrane domain structures to explore functional mechanisms

2020 ◽  
Author(s):  
Katherine E. Huffer ◽  
Antoniya A. Aleksandrova ◽  
Andrés Jara-Oseguera ◽  
Lucy R. Forrest ◽  
Kenton J. Swartz
Keyword(s):  
Transmembrane Domain ◽  
Ion Selectivity ◽  
Structural Data ◽  
Trp Channel ◽  
Structural Basis ◽  
Global Alignment ◽  
Functional Studies ◽  
Domain Structures ◽  
Mechanistic Basis ◽  
Channel Structures

AbstractThe recent proliferation of published TRP channel structures provides a foundation for understanding the diverse functional properties of this important family of ion channel proteins. To facilitate mechanistic investigations, we constructed a structure-based alignment of the transmembrane domains of 120 TRP channel structures. Comparison of structures determined in the absence or presence of activating stimuli reveals similar constrictions in the central ion permeation pathway near the intracellular end of the S6 helices, pointing to a conserved cytoplasmic gate and suggesting that most available structures represent non-conducting states. Comparison of the ion selectivity filters towards the extracellular end of the pore supports existing hypotheses for mechanisms of ion selectivity. Also conserved to varying extents are hot spots for interactions with hydrophobic ligands, lipids and ions, as well as discrete alterations in helix conformations. This analysis therefore provides a framework for investigating the structural basis of TRP channel gating mechanisms and pharmacology, and, despite the large number of structures included, reveals the need for additional structural data and for more functional studies to establish the mechanistic basis of TRP channel function.

scholarly journals Author response: C. elegans avoids toxin-producing Streptomyces using a seven transmembrane domain chemosensory receptor

2017 ◽  
Author(s):  
Alan Tran ◽  
Angelina Tang ◽  
Colleen T O'Loughlin ◽  
Anthony Balistreri ◽  
Eric Chang ◽  
...  
Keyword(s):  
Transmembrane Domain ◽  
Author Response ◽  
C Elegans ◽  
Chemosensory Receptor

scholarly journals Author response: Structural basis for effector transmembrane domain recognition by type VI secretion system chaperones

2020 ◽  
Author(s):  
Shehryar Ahmad ◽  
Kara K Tsang ◽  
Kartik Sachar ◽  
Dennis Quentin ◽  
Tahmid M Tashin ◽  
...  
Keyword(s):  
Transmembrane Domain ◽  
Secretion System ◽  
Author Response ◽  
Structural Basis ◽  
Type Vi Secretion System ◽  
Type Vi Secretion

scholarly journals The Pivotal Roles of the Epithelial Membrane Protein Family in Cancer Invasiveness and Metastasis

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1620 ◽  
Author(s):  
Ahmat Amin ◽  
Shimizu ◽  
Ogita
Keyword(s):  
Cell Migration ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Transmembrane Domain ◽  
Small Gtpase ◽  
Migration And Invasion ◽  
Amino Acid Residues ◽  
Peripheral Myelin Protein 22 ◽  
Domain Structures ◽  
Cancer Invasiveness

The members of the family of epithelial membrane proteins (EMPs), EMP1, EMP2, and EMP3, possess four putative transmembrane domain structures and are composed of approximately 160 amino acid residues. EMPs are encoded by the growth arrest-specific 3 (GAS3)/peripheral myelin protein 22 kDa (PMP22) gene family. The GAS3/PMP22 family members play roles in cell migration, growth, and differentiation. Evidence indicates an association of these molecules with cancer progression and metastasis. Each EMP has pro- and anti-metastatic functions that are likely involved in the complex mechanisms of cancer progression. We have recently demonstrated that the upregulation of EMP1 expression facilitates cancer cell migration and invasion through the activation of a small GTPase, Rac1. The inoculation of prostate cancer cells overexpressing EMP1 into nude mice leads to metastasis to the lymph nodes and lungs, indicating that EMP1 contributes to metastasis. Pro-metastatic properties of EMP2 and EMP3 have also been proposed. Thus, targeting EMPs may provide new insights into their clinical utility. Here, we highlight the important aspects of EMPs in cancer biology, particularly invasiveness and metastasis, and describe recent therapeutic approaches.

scholarly journals Assessment of the transmembrane domain structures in GPCR Dock 2013 models

2018 ◽  
Vol 201 (3) ◽  
pp. 210-220 ◽  
Author(s):  
Ting Wang ◽  
Haiguang Liu ◽  
Yong Duan
Keyword(s):  
Transmembrane Domain ◽  
Domain Structures

scholarly journals A novel domain assembly routine for creating full-length models of membrane proteins from known domain structures

2017 ◽  
Author(s):  
Julia Koehler Leman ◽  
Richard Bonneau
Keyword(s):  
Membrane Proteins ◽  
Biological Function ◽  
Transmembrane Domain ◽  
Search Space ◽  
Full Length ◽  
Conformational Search ◽  
Membrane Domains ◽  
Native Structure ◽  
Domain Structures ◽  
Fragment Insertion

AbstractMembrane proteins composed of soluble and membrane domains are often studied one domain at a time. However, to understand the biological function of entire protein systems and their interactions with each other and drugs, knowledge of full-length structures or models is required. Although few computational methods exist that could potentially be used to model full-length constructs of membrane proteins, none of these methods are perfectly suited for the problem at hand. Existing methods either require an interface or knowledge of the relative orientations of the domains, are not designed for domain assembly, and none of them are developed for membrane proteins. Here we describe the first domain assembly protocol specifically designed for membrane proteins that assembles intra- and extracellular soluble domains and the transmembrane domain into models of the full-length membrane protein. Our protocol does not require an interface between the domains and samples possible domain orientations based on backbone dihedrals in the flexible linker regions, created via fragment insertion, while keeping the transmembrane domain fixed in the membrane. Our method, mp_domain_assembly, implemented in RosettaMP samples domain orientations close to the native structure and is best used in conjunction with experimental data to reduce the conformational search space.

Sign in / Sign up

Export Citation Format

Share Document