PDBsum entry 1ss2

Signaling protein

PDB id: 1ss2

Contents

Protein chain

68 a.a.

PDB id:

1ss2

Name:

Signaling protein

Title:

Solution structure of the second complement control protein (ccp) module of the gaba(b)r1a receptor, pro-119 cis conformer

Structure:

Gamma-aminobutyric acid type b receptor, subunit 1. Chain: a. Fragment: sushi 2 (residues 96-159). Synonym: gaba-b receptor 1, gaba-b-r1, gb1. Engineered: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: gabbr1. Expressed in: pichia pastoris. Expression_system_taxid: 4922.

NMR struc:

24 models

Authors:

S.Blein,D.Uhrin,B.O.Smith,J.H.White,P.N.Barlow

Key ref:

S.Blein et al. (2004). Structural analysis of the complement control protein (CCP) modules of GABA(B) receptor 1a: only one of the two CCP modules is compactly folded. J Biol Chem, 279, 48292-48306. PubMed id: 15304491 DOI: 10.1074/jbc.M406540200

Date:

23-Mar-04 Release date: 12-Oct-04

Protein chain

Q9Z0U4  (GABR1_RAT) -  Gamma-aminobutyric acid type B receptor subunit 1 from Rattus norvegicus

Seq: 960 a.a.

Struc: 68 a.a.*

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

DOI no: 10.1074/jbc.M406540200

J Biol Chem 279:48292-48306 (2004)

PubMed id: 15304491

Structural analysis of the complement control protein (CCP) modules of GABA(B) receptor 1a: only one of the two CCP modules is compactly folded.

S.Blein, R.Ginham, D.Uhrin, B.O.Smith, D.C.Soares, S.Veltel, R.A.McIlhinney, J.H.White, P.N.Barlow.

ABSTRACT

The gamma-aminobutyric acid type B (GABA(B)) receptor is a heterodimeric G-protein-coupled receptor. In humans, three splice variants of the GABA(B) receptor 1 (R1) subunit differ in having one, both, or neither of two putative complement control protein (CCP) modules at the extracellular N terminus, prior to the GABA-binding domain. The in vivo function of these predicted modules remains to be discovered, but a likely association with extracellular matrix proteins is intriguing. The portion of the GABA(B) R1a variant encompassing both of its CCP module-like sequences has been expressed, as have the sequences corresponding to each individual module. Each putative CCP module exhibits the expected pattern of disulfide formation. However, the second module (CCP2) is more compactly folded than the first, and the three-dimensional structure of this more C-terminal module (expressed alone) was solved on the basis of NMR-derived nuclear Overhauser effects. This revealed a strong similarity to previously determined CCP module structures in the regulators of complement activation. The N-terminal module (CCP1) displayed conformational heterogeneity under a wide range of conditions whether expressed alone or together with CCP2. Several lines of evidence indicated the presence of native disorder in CCP1, despite the fact that recombinant CCP1 contributes to binding to the extracellular matrix protein fibulin-2. Thus, we have shown that the two CCP modules of GABA(B) R1a have strikingly different structural properties, reflecting their different functions.

Selected figure(s)

Figure 5.
FIG. 5. CD spectra of GABA[B] R1a CCP modules. a and b, far- and near-UV CD spectra for CCP1, respectively; c and d, far- and near-UV for CCP2, respectively. CD spectra were collected under near physiological conditions (solid lines) and after incubation with 10 mM DTT (dashed lines), 20 mM DTT (dotted lines), or 6 M GdnHCl (dashed and dotted lines). deg, degrees.

Figure 9.
FIG. 9. Surface features of GABA[B] R1a CCP2. a, two side views rotated by 180° along the y axis depicting the GRASP (74) electrostatic surface rendition of trans-CCP2. Negatively charged (acidic) residues are colored red, and positively charged (basic) residues are colored blue (range of -5 to +5 kT where k = Boltzman's constant and T = temperature in Kelvins). b, lipophilic surface: two views rotated by 180° along the y axis depicting the MOLCAD (75) lipophilic surface rendition of trans-CCP2. The regions of high hydrophilicity are colored blue, and the regions of high lipophilicity (hydrophobicity) are colored brown.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 48292-48306) copyright 2004.

Figures were selected by an automated process.