Demonstration of a tandem pair of complement protein modules in GABAB receptor 1a

被引:59
作者
Hawrot, E
Xiao, YY
Shi, QL
Norman, D
Kirkitadze, M
Barlow, PN
机构
[1] Edinburgh Ctr Prot Technol, Edinburgh EH9 3JJ, Midlothian, Scotland
[2] Univ Dundee, Inst Med Sci, Dept Biochem, Dundee DD1 4HN, Scotland
[3] Brown Univ, Dept Mol Pharmacol Physiol & Biotechnol, Providence, RI 02912 USA
基金
英国惠康基金;
关键词
SCR; Sushi; GABA(B) receptor; epilepsy; drug target;
D O I
10.1016/S0014-5793(98)00794-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have subcloned and expressed the N-terminal portion of the recently sequenced metabotropic GABA receptor, GABA(B)R1a, This region of the receptor contains a complement protein-like amino acid sequence. The purified 140-residue recombinant protein fragment was soluble and stable. Mass spectrometry indicated formation of four disulfide bonds, as expected if two complement protein modules (CPs, also known as SCRs, Sushi domains) are formed. The circular dichroism spectrum was unusual and characteristic of CPs, Differential scanning calorimetry demonstrated a melting point (64 degrees C), and total enthalpy commensurate with two fully folded domains. We thus conclude that the la subtype of the GABAB receptor, but not the Ib subtype, contains a pair of CPs and we present a three-dimensional model of this region. (C) 1998 Federation of European Biochemical Societies.
引用
收藏
页码:103 / 108
页数:6
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