PDBsum entry: 1jad

Hydrolase

PDB id: 1jad

Contents

Protein chains

242 a.a. *

Ligands

SO4

Waters ×143

* Residue conservation analysis

PDB id:

1jad

Name:

Hydrolase

Title:

C-terminal domain of turkey plc-beta

Structure:

PhospholipasE C beta. Chain: a, b. Fragment: c-terminus. Synonym: plc-beta. Engineered: yes. Mutation: yes

Source:

Meleagris gallopavo. Turkey. Organism_taxid: 9103. Cell: erythrocyte. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.40Å R-factor: 0.254 R-free: 0.295

Authors:

A.U.Singer,G.L.Waldo,T.K.Harden,J.Sondek

Key ref:

A.U.Singer et al. (2002). A unique fold of phospholipase C-beta mediates dimerization and interaction with G alpha q. Nat Struct Biol, 9, 32-36. PubMed id: 11753430 DOI: 10.1038/nsb731

Date:

30-May-01 Release date: 28-Dec-01

Protein chains

Q91086  (Q91086_MELGA) -  Phospholipase C beta

Seq: 1211 a.a.

Struc: 242 a.a.

 Gene Ontology (GO) functional annotation 

• Biological process: lipid metabolic process (1 term)
• Biochemical function: calcium ion binding (2 terms)

DOI no: 10.1038/nsb731

Nat Struct Biol 9:32-36 (2002)

PubMed id: 11753430

A unique fold of phospholipase C-beta mediates dimerization and interaction with G alpha q.

A.U.Singer, G.L.Waldo, T.K.Harden, J.Sondek.

ABSTRACT

GTP-bound subunits of the Gq family of G alpha subunits directly activate phospholipase C-beta (PLC-beta) isozymes to produce the second messengers inositol 1,4,5-trisphosphate and diacylglycerol. PLC-betas are GTPase activating proteins (GAPs) that also promote the formation of GDP-bound, inactive G beta subunits. Both phospholipase activation by G alpha-GTP subunits and GAP activity require a C-terminal region unique to PLC-beta isozymes. The crystal structure of the C-terminal region from an avian PLC-beta, determined at 2.4 A resolution, reveals a novel fold composed almost entirely of three long helices forming a coiled-coil that dimerizes along its long axis in an antiparallel orientation. The dimer interface is extensive ( approximately 3,200 A(2)), and, based on gel exclusion chromatography, full length PLC-betas are dimeric, indicating that PLC-betas likely function as dimers. Sequence conservation, mutational data and molecular modeling show that an electrostatically positive surface of the dimer contains the major determinants for binding G beta q. Effector dimerization, as highlighted by PLC-betas, provides a viable mechanism for regulating signaling cascades linked to heterotrimeric G proteins.

Selected figure(s)

Figure 1.
Figure 1. Overall structure of the CT domain unique to PLC- s. a, Stereo view overlay of the experimental electron density generated using density-modified phases, contoured at 0.7 , with atoms from helices A (green), B and B' (red), and the N-terminus (light blue). b, The CT domain of turkey PLC- is all helical and dimeric. The helical elements within a monomer are colored green ( A and A'), red ( B and B') and yellow ( C and C'). C trace of the CTt dimer is presented in stereo with every 20^th residue labeled. c, Ribbon diagram of the CTt dimer with a rotation of -90° about the z-axis relative to the view in (b). d, Ribbon diagram of the CTt dimer with a rotation of 90° about the horizontal axis relative to (c). e, Sequence alignment of CT domains from PLC- isozymes. Helical elements from the CTt structure are overlayed, and the 34-amino acid deletion introduced to promote crystallization is indicated by triangles. Numbering corresponds to the amino acid positions in full length PLC- s, and every 10^th residue within PLC- t is indicated by a black dot. Residues mutated in the study of Kim et al.8 that affected PLC- 1 activation by G q are denoted by black circles in helices A and B. Residues involved in the dimer interface are indicated by blue ovals above them.

Figure 3.
Figure 3. Dimeric CTt is highly electrostatically polarized. Electropositive potential (blue) is localized to the center of the surface formed by A and B. Electronegative potential (red) is mainly localized to the C helices. The orientation of CTt is denoted by ribbon diagram (insert) and is identical to Fig. 1b.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2002, 9, 32-36) copyright 2002.

Figures were selected by an automated process.