1SS2

Solution structure of the second complement control protein (CCP) module of the GABA(B)R1a receptor, Pro-119 cis conformer

Summary for 1SS2

• Entry DOI: 10.2210/pdb1ss2/pdb
• Related: 1SRZ
• NMR Information: BMRB: 6166
• Descriptor: Gamma-aminobutyric acid type B receptor, subunit 1 (1 entity in total)
• Functional Keywords: gaba(b) receptor, cis-trans isomerisation, ccp module, sushi domain, short consensus repeat, signaling protein
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Cell membrane; Multi-pass membrane protein: Q9Z0U4
• Total number of polymer chains: 1
• Total formula weight: 7494.42

Authors

Blein, S.,Uhrin, D.,Smith, B.O.,White, J.H.,Barlow, P.N. (deposition date: 2004-03-23, release date: 2004-10-12, Last modification date: 2024-11-06)

Primary citation

Blein, S.,Ginham, R.,Uhrin, D.,Smith, B.O.,Soares, D.C.,Veltel, S.,McIlhinney, R.A.,White, J.H.,Barlow, P.N.
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, 2004

PubMed 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.

PubMed: 15304491
DOI: 10.1074/jbc.M406540200

Experimental method

SOLUTION NMR