Pentameric assembly of the Kv2.1 tetramerization domain

Zhen Xu; Saif Khan; Nicholas J Schnicker; Sheila Baker

doi:10.1107/S205979832200568X

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Pentameric assembly of the Kv2.1 tetramerization domain

Journal article

Open access

Peer reviewed

Pentameric assembly of the Kv2.1 tetramerization domain

Zhen Xu, Saif Khan, Nicholas J Schnicker and Sheila Baker

Acta crystallographica. Section D, Biological crystallography, Vol.78(6), pp.792-802

06/01/2022

DOI: 10.1107/S205979832200568X

PMCID: PMC9159280

PMID: 35647925

Appears in UI Libraries Support Open Access

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Abstract

The Kv family of voltage‐gated potassium channels regulate neuronal excitability. The biophysical characteristics of Kv channels can be matched to the needs of different neurons by forming homotetrameric or heterotetrameric channels within one of four subfamilies. The cytoplasmic tetramerization (T1) domain plays a major role in dictating the compatibility of different Kv subunits. The only Kv subfamily lacking a representative structure of the T1 domain is the Kv2 family. Here, X‐ray crystallography was used to solve the structure of the human Kv2.1 T1 domain. The structure is similar to those of other T1 domains, but surprisingly formed a pentamer instead of a tetramer. In solution the Kv2.1 T1 domain also formed a pentamer, as determined by inline SEC–MALS–SAXS and negative‐stain electron microscopy. The Kv2.1 T1–T1 interface involves electrostatic interactions, including a salt bridge formed by the negative charges in a previously described CDD motif, and inter‐subunit coordination of zinc. It is shown that zinc binding is important for stability. In conclusion, the Kv2.1 T1 domain behaves differently from the other Kv T1 domains, which may reflect the versatility of Kv2.1, which can assemble with the regulatory KvS subunits and scaffold ER–plasma membrane contacts.

Crystallography

Electron Microscopy

Zinc

Channels

Domains

Electrostatic properties

Excitability

Potassium channels (voltage-gated)

Zinc coordination

UIOWA OA Agreement

Details

Title: Subtitle: Pentameric assembly of the Kv2.1 tetramerization domain
Creators: Zhen Xu
Saif Khan
Nicholas J Schnicker
Sheila Baker
Resource Type: Journal article
Publication Details: Acta crystallographica. Section D, Biological crystallography, Vol.78(6), pp.792-802
DOI: 10.1107/S205979832200568X
PMID: 35647925
PMCID: PMC9159280
NLM abbreviation: Acta Crystallogr D Biol Crystallogr
ISSN: 0907-4449
eISSN: 1399-0047
Publisher: Wiley
Grant note: DOI: 10.13039/100000057, name: National Institute of General Medical Sciences, award: P30 GM138395
Language: English
Date published: 06/01/2022
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Biochemistry and Molecular Biology; Medicine Administration; University College Courses; Ophthalmology and Visual Sciences
Record Identifier: 9984259954802771

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