LOCALIZATION OF THE THYROXINE BINDING-SITES IN APOLIPOPROTEIN-B-100 OF HUMAN LOW-DENSITY LIPOPROTEINS

被引:26
作者
BENVENGA, S
CAHNMANN, HJ
ROBBINS, J
机构
[1] NIDDKD,CLIN ENDOCRINOL BRANCH,BLDG 10,ROOM 8N315,BETHESDA,MD 20892
[2] UNIV MESSINA,SCH MED,IST CLIN MED 1,I-98100 MESSINA,ITALY
关键词
D O I
10.1210/endo-127-5-2241
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
By photoaffinity labeling human low density lipoproteins (LDL) with [125I]T4we confirmed our previous observation that of the three T4 binding sites of apolipoprotein B-100 (apoB-100) one is in its 26% NH2-terminal portion [apoB- 26, the 140 kDa fragment, residues 1-1297] and two in the remaining 74% COOH portion (apoB-74, 410 kDa, residues 1298-4536). We now show that of these two sites one is in the NH2portion of apoB-74 (apoB-44, 240 kDa, residues 1298-3249) and the other in the nonoverlapping COOH portion (apoB-30, 170 kDa, residues 3250-4536).ApoB-100 contains 13 binding sites for heparin, a known inhibitor of T4binding to the major T4carrier plasma proteins; however, heparin failed to inhibit T4binding to apoB-100 and fragments thereof. The same failure was seen with three monoclonal antibodies (MAbs), 4G3, 5E11, and 43 that block totally or partially LDL binding to the LDL receptor [respective epitopes at residues 2980-3084 (apoB-44), 3441-3569, and 4027- 4081 (apoB-30)]. Of the other 3 MAbs, all without effect on LDL binding to the LDL receptor, [1D1, 2D8, and 16, respective epitopes at residues 474-539 (apoB-26), 1438-1481 (apoB-44), and 4154-4189 (apoB-30)], only two (MAbs 1D1 and 2D8) inhibited T4binding (21 to 39%).We conclude that the three T4-binding sites of apoB-100 are outside the LDL receptor binding domain, distant from the heparin binding sites and, assuming no allosteric effects, in the vicinity of residues 474-539 (T4site of apoB-26), 1438-1481 (T4site of apoB-44), and in the C terminal quarter of apoB-30. © 1990 by The Endocrine Society.
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页码:2241 / 2246
页数:6
相关论文
共 22 条
[1]   BINDING OF THYROXINE TO HUMAN-PLASMA LOW-DENSITY LIPOPROTEIN THROUGH SPECIFIC INTERACTION WITH APOLIPOPROTEIN-B (APOB-100) [J].
BENVENGA, S ;
CAHNMANN, H ;
GREGG, R ;
ROBBINS, J .
BIOCHIMIE, 1989, 71 (02) :263-268
[2]   CHARACTERIZATION OF THE BINDING OF THYROXINE TO HIGH-DENSITY LIPOPROTEINS AND APOLIPOPROTEINS A-I [J].
BENVENGA, S ;
CAHNMANN, HJ ;
GREGG, RE ;
ROBBINS, J .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1989, 68 (06) :1067-1072
[3]   BINDING OF THYROID-HORMONES TO HUMAN-PLASMA LIPOPROTEINS [J].
BENVENGA, S ;
GREGG, RE ;
ROBBINS, J .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1988, 67 (01) :6-16
[4]   ENHANCEMENT OF THYROXINE ENTRY INTO LOW-DENSITY LIPOPROTEIN (LDL) RECEPTOR-COMPETENT FIBROBLASTS BY LDL - AN ADDITIONAL MODE OF ENTRY OF THYROXINE INTO CELLS [J].
BENVENGA, S ;
ROBBINS, J .
ENDOCRINOLOGY, 1990, 126 (02) :933-941
[5]  
BLAKE CCF, 1977, NATURE, V268, P115, DOI 10.1038/268115a0
[6]  
CARDIN AD, 1984, J BIOL CHEM, V259, P8522
[7]  
CARDIN AD, 1986, J BIOL CHEM, V261, P6744
[8]   PHYSICAL-CHEMICAL INTERACTION OF HEPARIN AND HUMAN-PLASMA LOW-DENSITY LIPOPROTEINS [J].
CARDIN, AD ;
RANDALL, CJ ;
HIROSE, N ;
JACKSON, RL .
BIOCHEMISTRY, 1987, 26 (17) :5513-5518
[9]   COMPLETE AMINO-ACID-SEQUENCE OF HUMAN THYROXINE-BINDING GLOBULIN DEDUCED FROM CLONED DNA - CLOSE HOMOLOGY TO THE SERINE ANTIPROTEASES [J].
FLINK, IL ;
BAILEY, TJ ;
GUSTAFSON, TA ;
MARKHAM, BE ;
MORKIN, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (20) :7708-7712
[10]   ISOLATION AND CHARACTERIZATION OF 4 HEPARIN-BINDING CYANOGEN-BROMIDE PEPTIDES OF HUMAN-PLASMA APOLIPOPROTEIN-B [J].
HIROSE, N ;
BLANKENSHIP, DT ;
KRIVANEK, MA ;
JACKSON, RL ;
CARDIN, AD .
BIOCHEMISTRY, 1987, 26 (17) :5505-5512