SEQUENCES DIRECTING DIHYDROLIPOAMIDE DEHYDROGENASE(E3) BINDING ARE LOCATED ON THE 2-OXOGLUTARATE DEHYDROGENASE(E1) COMPONENT OF THE MAMMALIAN 2-OXOGLUTARATE DEHYDROGENASE MULTIENZYME COMPLEX

被引:35
作者
RICE, JE
DUNBAR, B
LINDSAY, JG
机构
[1] UNIV GLASGOW, DEPT BIOCHEM, GLASGOW G12 8QQ, SCOTLAND
[2] UNIV ABERDEEN MARISCHAL COLL, DEPT MOLEC & CELL BIOL, ABERDEEN AB9 1AS, SCOTLAND
关键词
E1; COMPONENT; E3; BINDING; LIPOYL-LIKE DOMAIN; 2-OXOGLUTARATE DEHYDROGENASE COMPLEX;
D O I
10.1002/j.1460-2075.1992.tb05400.x
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
Sequences located in the N-terminal region of the high M(r) 2-oxoglutarate dehydrogenase (E1) enzyme of the mammalian 2-oxoglutarate dehydrogenase multienzyme complex (OGDC) exhibit significant similarity with corresponding sequences from the lipoyl domains of the dihydrolipoamide acetyltransferase (E2) and protein X components of eukaryotic pyruvate dehydrogenase complexes (PDCs). Two additional features of this region of E1 resemble lipoyl domains: (i) it is readily released by trypsin, generating a small N-terminal peptide with an apparent M(r) value of 10 000 and a large stable 100 000 M(r) fragment (E1') and (ii) it is highly immunogenic, inducing the bulk of the antibody response to intact E1. This 'lipoyl-like' domain lacks a functional lipoamide group. Selective but extensive degradation of E1 with proteinase Arg C or specific conversion of E1 to E1' with trypsin both cause loss of overall OGDC function although the E1' fragment retains full catalytic activity. Removal of this small N-terminal peptide promotes the dissociation of dihydrolipoamide dehydrogenase (E3) from the E2 core assembly and also affects the stability of E1 interaction. Thus, structural roles which are mediated by a specific gene product, protein X in PDC and possibly also the E2 subunit, are performed by similar structural elements located on the E1 enzyme of the OGDC.
引用
收藏
页码:3229 / 3235
页数:7
相关论文
共 34 条
[1]   ALPHA-KETO ACID DEHYDROGENASE COMPLEXES .16. STUDIES ON SUBUNIT STRUCTURE OF PYRUVATE DEHYDROGENASE COMPLEXES FROM BOVINE KIDNEY AND HEART [J].
BARRERA, CR ;
REED, LJ ;
LINN, TC ;
MUNK, P ;
NAMIHIRA, G ;
ELEY, MH ;
HAMILTON, L .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1972, 148 (02) :343-+
[2]   CLONING AND NUCLEOTIDE-SEQUENCE OF THE GENE FOR PROTEIN-X FROM SACCHAROMYCES-CEREVISIAE [J].
BEHAL, RH ;
BROWNING, KS ;
HALL, TB ;
REED, LJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (22) :8732-8736
[3]  
BOUSFIELD GR, 1988, J BIOL CHEM, V263, P12602
[4]   SELECTIVE INACTIVATION OF TRANSACYLASE COMPONENTS OF 2-OXO ACID DEHYDROGENASE MULTIENZYME COMPLEXES OF ESCHERICHIA-COLI [J].
BROWN, JP ;
PERHAM, RN .
BIOCHEMICAL JOURNAL, 1976, 155 (02) :419-&
[5]  
CHARTIER F, 1989, J BIOL CHEM, V264, P17006
[6]   IMMUNOLOGY, BIOSYNTHESIS AND INVIVO ASSEMBLY OF THE BRANCHED-CHAIN 2-OXOACID DEHYDROGENASE COMPLEX FROM BOVINE KIDNEY [J].
CLARKSON, GHD ;
LINDSAY, JG .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1991, 196 (01) :95-100
[7]   SEQUENCE-SPECIFIC H-1-NMR ASSIGNMENTS AND SECONDARY STRUCTURE OF THE LIPOYL DOMAIN OF THE BACILLUS-STEAROTHERMOPHILUS PYRUVATE-DEHYDROGENASE MULTIENZYME COMPLEX [J].
DARDEL, F ;
LAUE, ED ;
PERHAM, RN .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1991, 201 (01) :203-209
[8]   COMPONENT-X - AN IMMUNOLOGICALLY DISTINCT POLYPEPTIDE ASSOCIATED WITH MAMMALIAN PYRUVATE-DEHYDROGENASE MULTI-ENZYME COMPLEX [J].
DEMARCUCCI, O ;
LINDSAY, JG .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1985, 149 (03) :641-648
[9]  
DEMARCUCCI OGL, 1986, EUR J BIOCHEM, V158, P587
[10]   LOW IMMUNOGENICITY OF THE COMMON LIPOAMIDE DEHYDROGENASE SUBUNIT (E3) OF MAMMALIAN PYRUVATE-DEHYDROGENASE AND 2-OXOGLUTARATE DEHYDROGENASE MULTIENZYME COMPLEXES [J].
DEMARCUCCI, OL ;
HUNTER, A ;
LINDSAY, JG .
BIOCHEMICAL JOURNAL, 1985, 226 (02) :509-517