PDBsum entry 6j8h

Membrane protein

PDB id: 6j8h

Contents

Protein chains

120 a.a.

1140 a.a.

173 a.a.

Ligands

NAG-NAG ×2

NAG ×7

9SL

PDB id:

6j8h

Name:

Membrane protein

Title:

Structure of human voltage-gated sodium channel nav1.7 in complex with auxiliary beta subunits, huwentoxin-iv and saxitoxin (y1755 down)

Structure:

Sodium channel subunit beta-2. Chain: c. Engineered: yes. Sodium channel protein type 9 subunit alpha. Chain: a. Synonym: neuroendocrine sodium channel,hne-na,peripheral sodium channel 1,pn1,sodium channel protein type ix subunit alpha,voltage- gated sodium channel subunit alpha nav1.7. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: scn2b, unq326/pro386. Expressed in: homo sapiens. Expression_system_taxid: 9606. Gene: scn9a, nena. Gene: scn1b. Expression_system_taxid: 9606

Authors:

H.Shen,D.Liu,J.Lei,N.Yan

Key ref:

H.Shen et al. (2019). Structures of human Na_v1.7 channel in complex with auxiliary subunits and animal toxins. Science, 363, 1303-1308. PubMed id: 30765606 DOI: 10.1126/science.aaw2493

Date:

19-Jan-19 Release date: 27-Feb-19

Protein chain

O60939  (SCN2B_HUMAN) -  Sodium channel regulatory subunit beta-2 from Homo sapiens

Seq: 215 a.a.

Struc: 120 a.a.

Protein chain

Q15858  (SCN9A_HUMAN) -  Sodium channel protein type 9 subunit alpha from Homo sapiens

Seq: 1988 a.a.

Struc: 1140 a.a.*

Protein chain

Q07699  (SCN1B_HUMAN) -  Sodium channel regulatory subunit beta-1 from Homo sapiens

Seq: 218 a.a.

Struc: 173 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1126/science.aaw2493

Science 363:1303-1308 (2019)

PubMed id: 30765606

Structures of human Na_v1.7 channel in complex with auxiliary subunits and animal toxins.

H.Shen, D.Liu, K.Wu, J.Lei, N.Yan.

ABSTRACT

Voltage-gated sodium channel Na_v1.7 represents a promising target for pain relief. Here we report the cryo-electron microscopy structures of the human Na_v1.7-β1-β2 complex bound to two combinations of pore blockers and gating modifier toxins (GMTs), tetrodotoxin with protoxin-II and saxitoxin with huwentoxin-IV, both determined at overall resolutions of 3.2 angstroms. The two structures are nearly identical except for minor shifts of voltage-sensing domain II (VSD_II), whose S3-S4 linker accommodates the two GMTs in a similar manner. One additional protoxin-II sits on top of the S3-S4 linker in VSD_IV The structures may represent an inactivated state with all four VSDs "up" and the intracellular gate closed. The structures illuminate the path toward mechanistic understanding of the function and disease of Na_v1.7 and establish the foundation for structure-aided development of analgesics.