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Structural conservation of ion conduction pathways in K channels and glutamate receptors.

Publication ,  Journal Article
Wood, MW; VanDongen, HM; VanDongen, AM
Published in: Proc Natl Acad Sci U S A
May 23, 1995

Single channel recordings demonstrate that ion channels switch stochastically between an open and a closed pore conformation. In search of a structural explanation for this universal open/close behavior, we have uncovered a striking degree of amino acid homology across the pore-forming regions of voltage-gated K channels and glutamate receptors. This suggested that the pores of these otherwise unrelated classes of channels could be structurally conserved. Strong experimental evidence supports a hairpin structure for the pore-forming region of K channels. Consequently, we hypothesized the existence of a similar structure for the pore of glutamate receptors. In ligand-gated channels, the pore is formed by M2, the second of four putative transmembrane segments. A hairpin structure for M2 would affect the subsequent membrane topology, inverting the proposed orientation of the next segments, M3. We have tested this idea for the NR1 subunit of the N-methyl-D-aspartate receptor. Mutations that affected the glycosylation pattern of the NR1 subunit localize both extremes of the M3-M4 linker to the extracellular space. Whole cell currents and apparent agonist affinities were not affected by these mutations. Therefore it can be assumed that they represent the native transmembrane topology. The extracellular assignment of the M3-M4 linker challenged the current topology model by inverting M3. Taken together, the amino acid homology and the new topology suggest that the pore-forming M2 segment of glutamate receptors does not transverse the membrane but, rather, forms a hairpin structure, similar to that found in K channels.

Duke Scholars

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

May 23, 1995

Volume

92

Issue

11

Start / End Page

4882 / 4886

Location

United States

Related Subject Headings

  • Xenopus laevis
  • Sequence Homology, Amino Acid
  • Recombinant Proteins
  • Receptors, Serotonin
  • Receptors, Nicotinic
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Glutamate
  • Receptors, GABA
  • Protein Structure, Secondary
  • Potassium Channels
 

Citation

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MLA
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Wood, M. W., VanDongen, H. M., & VanDongen, A. M. (1995). Structural conservation of ion conduction pathways in K channels and glutamate receptors. Proc Natl Acad Sci U S A, 92(11), 4882–4886. https://doi.org/10.1073/pnas.92.11.4882
Wood, M. W., H. M. VanDongen, and A. M. VanDongen. “Structural conservation of ion conduction pathways in K channels and glutamate receptors.Proc Natl Acad Sci U S A 92, no. 11 (May 23, 1995): 4882–86. https://doi.org/10.1073/pnas.92.11.4882.
Wood MW, VanDongen HM, VanDongen AM. Structural conservation of ion conduction pathways in K channels and glutamate receptors. Proc Natl Acad Sci U S A. 1995 May 23;92(11):4882–6.
Wood, M. W., et al. “Structural conservation of ion conduction pathways in K channels and glutamate receptors.Proc Natl Acad Sci U S A, vol. 92, no. 11, May 1995, pp. 4882–86. Pubmed, doi:10.1073/pnas.92.11.4882.
Wood MW, VanDongen HM, VanDongen AM. Structural conservation of ion conduction pathways in K channels and glutamate receptors. Proc Natl Acad Sci U S A. 1995 May 23;92(11):4882–4886.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

May 23, 1995

Volume

92

Issue

11

Start / End Page

4882 / 4886

Location

United States

Related Subject Headings

  • Xenopus laevis
  • Sequence Homology, Amino Acid
  • Recombinant Proteins
  • Receptors, Serotonin
  • Receptors, Nicotinic
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Glutamate
  • Receptors, GABA
  • Protein Structure, Secondary
  • Potassium Channels