PDBsum entry 3j41

Transport protein/calcium binding

PDB id: 3j41

Contents

Protein chains

233 a.a.

143 a.a.

Metals

_CA ×8

PDB id:

3j41

Name:

Transport protein/calcium binding

Title:

Pseudo-atomic model of the aquaporin-0/calmodulin complex derived from electron microscopy

Structure:

Lens fiber major intrinsic protein. Chain: a, b, c, d. Fragment: see remark 999. Synonym: aquaporin-0. Calmodulin. Chain: e, f. Synonym: cam. Engineered: yes

Source:

Ovis aries. Sheep. Organism_taxid: 9940. Tissue: eye lens. Homo sapiens. Human. Organism_taxid: 9606. Gene: calm1, calm, cam, cam1, calm2, cam2, camb, calm3, calml2, cam3, camc, camiii.

Authors:

S.L.Reichow,D.M.Clemens,J.A.Freites,K.L.Nemeth-Cahalan,M.Heyden, D.J.Tobias,J.E.Hall,T.Gonen

Key ref:

S.L.Reichow et al. (2013). Allosteric mechanism of water-channel gating by Ca2+-calmodulin. Nat Struct Biol, 20, 1085-1092. PubMed id: 23893133 DOI: 10.1038/nsmb.2630

Date:

31-May-13 Release date: 31-Jul-13

Protein chains

Q6J8I9  (MIP_SHEEP) -  Lens fiber major intrinsic protein from Ovis aries

Seq: 263 a.a.

Struc: 233 a.a.*

Protein chains

P0DP23  (CALM1_HUMAN) -  Calmodulin-1 from Homo sapiens

Seq: 149 a.a.

Struc: 143 a.a.

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DOI no: 10.1038/nsmb.2630

Nat Struct Biol 20:1085-1092 (2013)

PubMed id: 23893133

Allosteric mechanism of water-channel gating by Ca2+-calmodulin.

S.L.Reichow, D.M.Clemens, J.A.Freites, K.L.Németh-Cahalan, M.Heyden, D.J.Tobias, J.E.Hall, T.Gonen.

ABSTRACT

Calmodulin (CaM) is a universal regulatory protein that communicates the presence of calcium to its molecular targets and correspondingly modulates their function. This key signaling protein is important for controlling the activity of hundreds of membrane channels and transporters. However, understanding of the structural mechanisms driving CaM regulation of full-length membrane proteins has remained elusive. In this study, we determined the pseudoatomic structure of full-length mammalian aquaporin-0 (AQP0, Bos taurus) in complex with CaM, using EM to elucidate how this signaling protein modulates water-channel function. Molecular dynamics and functional mutation studies reveal how CaM binding inhibits AQP0 water permeability by allosterically closing the cytoplasmic gate of AQP0. Our mechanistic model provides new insight, only possible in the context of the fully assembled channel, into how CaM regulates multimeric channels by facilitating cooperativity between adjacent subunits.