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Structure paper

TitleMolecular structures of the human Slo1 K channel in complex with β4.
Journal, issue, pagesElife, Vol. 8, Year 2019
Publish dateDec 9, 2019
AuthorsXiao Tao / Roderick MacKinnon /
PubMed AbstractSlo1 is a Ca- and voltage-activated K channel that underlies skeletal and smooth muscle contraction, audition, hormone secretion and neurotransmitter release. In mammals, Slo1 is regulated by ...Slo1 is a Ca- and voltage-activated K channel that underlies skeletal and smooth muscle contraction, audition, hormone secretion and neurotransmitter release. In mammals, Slo1 is regulated by auxiliary proteins that confer tissue-specific gating and pharmacological properties. This study presents cryo-EM structures of Slo1 in complex with the auxiliary protein, β4. Four β4, each containing two transmembrane helices, encircle Slo1, contacting it through helical interactions inside the membrane. On the extracellular side, β4 forms a tetrameric crown over the pore. Structures with high and low Ca concentrations show that identical gating conformations occur in the absence and presence of β4, implying that β4 serves to modulate the relative stabilities of 'pre-existing' conformations rather than creating new ones. The effects of β4 on scorpion toxin inhibition kinetics are explained by the crown, which constrains access but does not prevent binding.
External linksElife / PubMed:31815672 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 4.0 Å
Structure data

21025

6v22

EMDB-21025, PDB-6v22:
Cryo-EM structure of Ca2+-bound hsSlo1-beta4 channel complex
Method: EM (single particle) / Resolution: 3.2 Å

21028

6v35

EMDB-21028, PDB-6v35:
Cryo-EM structure of Ca2+-free hsSlo1-beta4 channel complex
Method: EM (single particle) / Resolution: 3.5 Å

21029

6v38

EMDB-21029, PDB-6v38:
Cryo-EM structure of Ca2+-bound hsSlo1 channel
Method: EM (single particle) / Resolution: 3.8 Å

21036

6v3g

EMDB-21036, PDB-6v3g:
Cryo-EM structure of Ca2+-free hsSlo1 channel
Method: EM (single particle) / Resolution: 4.0 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-CA:
Unknown entry

ChemComp-POV:
(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipid*YM / POPC

ChemComp-CLR:
CHOLESTEROL / Cholesterol

ChemComp-K:
Unknown entry

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-PGW:
(1R)-2-{[(S)-{[(2S)-2,3-dihydroxypropyl]oxy}(hydroxy)phosphoryl]oxy}-1-[(hexadecanoyloxy)methyl]ethyl / phospholipid*YM / Phosphatidylglycerol

Source
  • homo sapiens (human)
KeywordsTRANSPORT PROTEIN / High conductance Ca2+-activated K+ channel / Slo1 channel / BK channel / MaxiK channel / Slo1 beta subunit / beta4 subunit

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