Yin Yao Dong

Prof. Yin Yao Dong

orcid

Research Focus & Metrics

Academic Career Length

14Years (2013-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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13 March 2015 in Science
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Journal Article
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Yin Yao DongYin Yao Dong
Yin Yao Dong
APAshley C. W. Pike
Ashley C. W. Pike
AMAlexandra Mackenzie
Alexandra Mackenzie
CMConor McClenaghan
Conor McClenaghan
PAPrafulla Aryal
Prafulla Aryal
ECElisabeth P. Carpenter
Elisabeth P. Carpenter
A sensitive regulator of cellular potassium: A class of potassium channels called K2P channels modulates resting membrane potential in most cells. The channels are regulated by multiple ligands, including the antidepressant drug Prozac, as well as factors such as mechanical stretch and voltage. Dong et al. determined the structure of the human K2P channel, TREK-2, in two conformations and bound to a metabolite of Prozac. The structures show how ligand binding or mechanical stretch might induce switching between the states. Although both states have open channels, one appears primed for gating. A Prozac metabolite binds to the primed state and prevents conformational switching. K2P channels are not a target of Prozac, but their inhibition may contribute to side effects. Science , this issue p. 1256

29 March 2013 in Science
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Journal Article
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AQAndrew Quigley
Andrew Quigley
Yin Yao DongYin Yao Dong
Yin Yao Dong
APAshley C. W. Pike
Ashley C. W. Pike
LDLiang Dong
Liang Dong
LSLeela Shrestha
Leela Shrestha
ECElisabeth P. Carpenter
Elisabeth P. Carpenter
Lamin Loppers: The nuclear lamina provides mechanical stability to the nuclear envelope and is involved in regulation of cellular processes such as DNA replication. Defects in the nuclear lamina lead to diseases such as progeria and metabolic disorders. One of the components of the nuclear lamina, lamin A, undergoes a complex maturation process. A key player is an inner nuclear membrane zinc metalloprotease (ZMP) that is responsible for two proteolysis steps (see the Perspective by Michaelis and Hrycyna ). Quigley et al. (p. 1604 ) report the crystal structure of human ZMPSTE24 and Pryor et al. (p. 1600 ) that of the yeast homolog Ste24p. The structures provide insight into the mechanism of catalysis and into why mutations in ZMPSTE24 lead to laminopathies.

1 November 2018 in Cell
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Journal Article
Open access
Yin Yao DongYin Yao Dong
Yin Yao Dong
HWHua Wang
Hua Wang
APAshley C.W. Pike
Ashley C.W. Pike
SCStephen A. Cochrane
Stephen A. Cochrane
SHSadra Hamedzadeh
Sadra Hamedzadeh
ECElisabeth P. Carpenter
Elisabeth P. Carpenter
Protein N-glycosylation is a widespread post-translational modification. The first committed step in this process is catalysed by dolichyl-phosphate N-acetylglucosamine-phosphotransferase DPAGT1 (GPT/E.C. 2.7.8.15). Missense DPAGT1 variants cause congenital myasthenic syndrome and disorders of glycosylation. In addition, naturally-occurring bactericidal nucleoside analogues such as tunicamycin are toxic to eukaryotes due to DPAGT1 inhibition, preventing their clinical use. Our structures of DPAGT1 with the substrate UDP-GlcNAc and tunicamycin reveal substrate binding modes, suggest a mechanism of catalysis, provide an understanding of how mutations modulate activity (thus causing disease) and allow design of non-toxic "lipid-altered" tunicamycins. The structure-tuned activity of these analogues against several bacterial targets allowed the design of potent antibiotics for Mycobacterium tuberculosis, enabling treatment in vitro, in cellulo and in vivo, providing a promising new class of antimicrobial drug.

1 May 2017 in Structure
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Journal Article
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PAPrafulla Aryal
Prafulla Aryal
VJViwan Jarerattanachat
Viwan Jarerattanachat
MCMichael V. Clausen
Michael V. Clausen
MSMarcus Schewe
Marcus Schewe
CMConor McClenaghan
Conor McClenaghan
STStephen Tucker
Stephen Tucker
The mechanosensitive two-pore domain (K2P) K+ channels (TREK-1, TREK-2, and TRAAK) are important for mechanical and thermal nociception. However, the mechanisms underlying their gating by membrane stretch remain controversial. Here we use molecular dynamics simulations to examine their behavior in a lipid bilayer. We show that TREK-2 moves from the "down" to "up" conformation in direct response to membrane stretch, and examine the role of the transmembrane pressure profile in this process. Furthermore, we show how state-dependent interactions with lipids affect the movement of TREK-2, and how stretch influences both the inner pore and selectivity filter. Finally, we present functional studies that demonstrate why direct pore block by lipid tails does not represent the principal mechanism of mechanogating. Overall, this study provides a dynamic structural insight into K2P channel mechanosensitivity and illustrates how the structure of a eukaryotic mechanosensitive ion channel responds to changes in forces within the bilayer.

3 October 2019 in eLife
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Journal Article
Open access
XYXiaodi Yu
Xiaodi Yu
OPOlga Plotnikova
Olga Plotnikova
PBPaul D Bonin
Paul D Bonin
TSTimothy A Subashi
Timothy A Subashi
TMThomas J McLellan
Thomas J McLellan
SHSeungil Han
Seungil Han
Alanine-serine-cysteine transporter 2 (ASCT2, SLC1A5) is the primary transporter of glutamine in cancer cells and regulates the mTORC1 signaling pathway. The SLC1A5 function involves finely tuned orchestration of two domain movements that include the substrate-binding transport domain and the scaffold domain. Here, we present cryo-EM structures of human SLC1A5 and its complex with the substrate, L-glutamine in an outward-facing conformation. These structures reveal insights into the conformation of the critical ECL2a loop which connects the two domains, thus allowing rigid body movement of the transport domain throughout the transport cycle. Furthermore, the structures provide new insights into substrate recognition, which involves conformational changes in the HP2 loop. A putative cholesterol binding site was observed near the domain interface in the outward-facing state. Comparison with the previously determined inward-facing structure of SCL1A5 provides a basis for a more integrated understanding of substrate recognition and transport mechanism in the SLC1 family.

5 August 2020 in Journal of Inherited Metabolic Disease
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Journal Article
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BNBobby G. Ng
Bobby G. Ng
EEErik A. Eklund
Erik A. Eklund
SSSergey A. Shiryaev
Sergey A. Shiryaev
Yin Yao DongYin Yao Dong
Yin Yao Dong
MAMary‐Alice Abbott
Mary‐Alice Abbott
HFHudson Freeze
Hudson Freeze