Structure of voltage-modulated sodium-selective NALCN-FAM155A channel complex

Wu, Jing-Xiang; Chen, Lei

doi:10.1101/2020.07.26.221747

Cited by 7 publications

(11 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Initial model was generated using cryoSPARC 37 . Particles were subjected to multi-reference 3D classification 38,39 and random-phase 3D classification 38,39 . Phase-randomized models were generated from the model obtained from previous refinement using randomize software (from the lab of Nikolaus Grigorieff).…”

Section: Methodsmentioning

confidence: 99%

Structures of human dual oxidase 1 complex in low-calcium and high-calcium states

Liu

Song

et al. 2021

Nat Commun

Self Cite

View full text Add to dashboard Cite

Dual oxidases (DUOXs) produce hydrogen peroxide by transferring electrons from intracellular NADPH to extracellular oxygen. They are involved in many crucial biological processes and human diseases, especially in thyroid diseases. DUOXs are protein complexes co-assembled from the catalytic DUOX subunits and the auxiliary DUOXA subunits and their activities are regulated by intracellular calcium concentrations. Here, we report the cryo-EM structures of human DUOX1-DUOXA1 complex in both high-calcium and low-calcium states. These structures reveal the DUOX1 complex is a symmetric 2:2 hetero-tetramer stabilized by extensive inter-subunit interactions. Substrate NADPH and cofactor FAD are sandwiched between transmembrane domain and the cytosolic dehydrogenase domain of DUOX. In the presence of calcium ions, intracellular EF-hand modules might enhance the catalytic activity of DUOX by stabilizing the dehydrogenase domain in a conformation that allows electron transfer.

show abstract

Section: Methodsmentioning

confidence: 99%

Structures of human dual oxidase 1 complex in low-calcium and high-calcium states

Liu

Song

et al. 2021

Nat Commun

Self Cite

View full text Add to dashboard Cite

show abstract

“…These particles were subjected to Ab-initio reconstruction in cryoSPARC-2.9.0 (Punjani et al, 2017), specifying four output classes. The best class with 245,031 particles was selected, then subjected to a resolutionbased classification workflow similar to a previous study (Kang et al, 2020). In brief, 40…”

Section: Image Processingmentioning

confidence: 99%

Analysis of the mechanosensor channel functionality of TACAN

Niu

Tao

Vaisey

et al. 2021

eLife

View full text Add to dashboard Cite

Mechanosensitive ion channels mediate transmembrane ion currents activated by mechanical forces. A mechanosensitive ion channel called TACAN was recently reported. We began to study TACAN with the intent to understand how it senses mechanical forces and functions as an ion channel. Using cellular patch-recording methods we failed to identify mechanosensitive ion channel activity. Using membrane reconstitution methods we found that TACAN, at high protein concentrations, produces heterogeneous conduction levels that are not mechanosensitive and are most consistent with disruptions of the lipid bilayer. We determined the structure of TACAN using single particle cryo-EM and observe that it forms a symmetrical dimeric transmembrane protein. Each protomer contains an intracellular-facing cleft with a coenzyme-A cofactor, confirmed by mass spectrometry. The TACAN protomers are related in 3-dimensional structure to a fatty acid elongase, ELOVL. Whilst its physiological function remains unclear, we anticipate that TACAN is not a mechanosensitive ion channel.

show abstract

“…Initial model was generated using cryoSPARC 34 . Particles were subjected to multi-reference 3D classification 35, 36 and random-phase 3D classification 35, 36 . Phase-randomized models were generated from the model obtained from previous refinement using randomize software (from the lab of Nikolaus Grigorieff).…”

Section: Methodsmentioning

confidence: 99%

Structure and mechanism of human dual oxidase 1 complex

Song

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Dual oxidases (DUOXs) produce hydrogen peroxide by transferring electrons from intracellular NADPH to extracellular oxygen. They are involved in many crucial biological processes and human diseases, especially in thyroid diseases. DUOXs are protein complexes co-assembled from the catalytic DUOX subunits and the auxiliary DUOXA subunits and their activities are regulated by intracellular calcium concentrations. Here, we report the cryo-EM structures of human DUOX1-DUOXA1 complex in both high-calcium and low-calcium states. These structures reveal the DUOX1 complex is a symmetric 2:2 hetero-tetramer stabilized by extensive inter-subunit interactions. Substrate NADPH and cofactor FAD are sandwiched between transmembrane domain and the cytosolic dehydrogenase domain of DUOX. In the presence of calcium ions, intracellular EF-hand modules enhance the catalytic activity of DUOX by stabilizing the dehydrogenase domain in a position that is optimal for electron transfer.

show abstract

Structure of voltage-modulated sodium-selective NALCN-FAM155A channel complex

Cited by 7 publications

References 51 publications

Structures of human dual oxidase 1 complex in low-calcium and high-calcium states

Structures of human dual oxidase 1 complex in low-calcium and high-calcium states

Analysis of the mechanosensor channel functionality of TACAN

Structure and mechanism of human dual oxidase 1 complex

Contact Info

Product

Resources

About