ArticleProtein science : a publication of the Protein Society2023
Photomodulation of the ASIC1a acidic pocket destabilizes the open state.
Article in Protein science : a publication of the Protein Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Mechanism of acid-sensing ion channel modulation by Hi1a.The Journal of general physiology · 2024Article
- Noncanonical Amino Acid Tools and Their Application to Membrane Protein Studies.Chemical reviews · 2024Review
- Genetic Code Expansion for Mechanistic Studies in Ion Channels: An (Un)natural Union of Chemistry and Biology.Chemical reviews · 2024Review
- A conserved peptide-binding pocket in HyNaC/ASIC ion channels.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Dynamic conformational changes of acid-sensing ion channels in different desensitizing conditions.Biophysical journal · 2024Article
- Photomodulation of the ASIC1a acidic pocket destabilizes the open state.Protein science : a publication of the Protein Society · 2023Article
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5 authors.
Funding
Abstract
Acid-sensing ion channels (ASICs) are important players in detecting extracellular acidification throughout the brain and body. ASICs have large extracellular domains containing two regions replete with acidic residues: the acidic pocket, and the palm domain. In the resting state, the acidic pocket is in an expanded conformation but collapses in low pH conditions as the acidic side chains are neutralized. Thus, extracellular acidification has been hypothesized to collapse the acidic pocket that, in turn, ultimately drives channel activation. However, several observations run counter to this idea. To explore how collapse or mobility of the acidic pocket is linked to channel gating, we employed two distinct tools. First, we incorporated the photocrosslinkable noncanonical amino acids (ncAAs) 4-azido-L-phenylalanine (AzF) or 4-benzoyl-L-phenylalanine (BzF) into several positions in the acidic pocket. At both E315 and Y318, AzF incorporation followed by UV irradiation led to right shifts in pH response curves and accelerations of desensitization and deactivation, consistent with restrictions of acidic pocket mobility destabilizing the open state. Second, we reasoned that because Cl
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