RECEPTOR-MODULATED IRON RELEASE FROM TRANSFERRIN - DIFFERENTIAL-EFFECTS ON N-TERMINAL AND C-TERMINAL SITES

被引:93
作者
BALI, PK
AISEN, P
机构
[1] YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT PHYSIOL & BIOPHYS,BRONX,NY 10461
[2] YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MED,BRONX,NY 10461
关键词
D O I
10.1021/bi00105a019
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
Iron release to PP(i) from N- and C-terminal monoferric transferrins and their complexes with transferrin receptor has been studied at pH 7.4 and 5.6 in 0.05 M HEPES or MES/0.1 M NaCl/0.01 M CHAPS at 25-degrees-C. The two sites exhibit kinetic heterogeneity in releasing iron. The N-terminal form is slightly less labile than its C-terminal counterpart at pH 7.4, but much more facile in releasing iron at pH 5.6. At pH 7.4, iron removal by 0.05 M pyrophosphate from each form of monoferric transferrin complexed to the receptor is considerably slower than from the corresponding free monoferric transferrin. However, at pH 5.6, complexation of transferrin to its receptor affects the two forms differently. The rate of iron release to 0.005 M pyrophosphate by the N-terminal species is substantially the same whether transferrin is free or bound to the receptor. In contrast, the C-terminal form releases iron much faster when complexed to the receptor than when free. Urea/PAGE analysis of iron removal from free and receptor-complexed diferric transferrin at pH 5.6 reveals that its C-terminal site is also more labile in the complex, but its N-terminal site is more labile in free diferric transferrin. Thus, the newly discovered role of transferrin receptor in modulating iron release from transferrin predominantly involves the C-terminal site. This observation helps explain the prevalence of circulating N-terminal monoferric transferrin in the human circulation.
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页码:9947 / 9952
页数:6
相关论文
共 38 条
[1]  
AISEN P, 1978, J BIOL CHEM, V253, P1930
[2]  
Aisen P, 1983, BIOL ASPECTS METALS, P67
[3]   APOLACTOFERRIN STRUCTURE DEMONSTRATES LIGAND-INDUCED CONFORMATIONAL CHANGE IN TRANSFERRINS [J].
ANDERSON, BF ;
BAKER, HM ;
NORRIS, GE ;
RUMBALL, SV ;
BAKER, EN .
NATURE, 1990, 344 (6268) :784-787
[4]   STRUCTURE OF HUMAN LACTOFERRIN AT 3.2-A RESOLUTION [J].
ANDERSON, BF ;
BAKER, HM ;
DODSON, EJ ;
NORRIS, GE ;
RUMBALL, SV ;
WATERS, JM ;
BAKER, EN .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (07) :1769-1773
[5]   MOLECULAR-STRUCTURE OF SERUM TRANSFERRIN AT 3.3-A RESOLUTION [J].
BAILEY, S ;
EVANS, RW ;
GARRATT, RC ;
GORINSKY, B ;
HASNAIN, S ;
HORSBURGH, C ;
JHOTI, H ;
LINDLEY, PF ;
MYDIN, A ;
SARRA, R ;
WATSON, JL .
BIOCHEMISTRY, 1988, 27 (15) :5804-5812
[6]   THE EFFECT OF SALTS ON THE KINETICS OF IRON RELEASE FROM N-TERMINAL AND C-TERMINAL MONOFERRIC-TRANSFERRINS [J].
BALDWIN, DA ;
DESOUSA, DMR .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1981, 99 (04) :1101-1107
[7]   THE EFFECT OF PH ON THE KINETICS OF IRON RELEASE FROM HUMAN TRANSFERRIN [J].
BALDWIN, DA ;
DESOUSA, DMR ;
VONWANDRUSZKA, RMA .
BIOCHIMICA ET BIOPHYSICA ACTA, 1982, 719 (01) :140-146
[8]   A NEW ROLE FOR THE TRANSFERRIN RECEPTOR IN THE RELEASE OF IRON FROM TRANSFERRIN [J].
BALI, PK ;
ZAK, O ;
AISEN, P .
BIOCHEMISTRY, 1991, 30 (02) :324-328
[9]   COOPERATIVITY AND HETEROGENEITY BETWEEN THE 2 BINDING-SITES OF DIFERRIC TRANSFERRIN DURING IRON REMOVAL BY PYROPHOSPHATE [J].
BALI, PK ;
HARRIS, WR .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1989, 111 (12) :4457-4461
[10]   KINETICS OF IRON REMOVAL FROM MONOFERRIC AND COBALT-LABELED MONOFERRIC HUMAN SERUM TRANSFERRIN BY NITRILOTRIS(METHYLENEPHOSPHONIC ACID) AND NITRILOTRIACETIC ACID [J].
BALI, PK ;
HARRIS, WR ;
NESSETTOLLEFSON, D .
INORGANIC CHEMISTRY, 1991, 30 (03) :502-508