Mapping of the binding of platelet-derived growth factor to distinct domains of the basement membrane proteins BM-40 and perlecan and distinction from the BM-40 collagen-binding epitope

被引:110
作者
Göhring, W
Sasaki, T
Heldin, CH
Timpl, R [1 ]
机构
[1] Max Planck Inst Biochem, D-82152 Martinsried, Germany
[2] Ludwig Inst Canc Res, Ctr Biomed, S-75124 Uppsala, Sweden
来源
EUROPEAN JOURNAL OF BIOCHEMISTRY | 1998年 / 255卷 / 01期
关键词
basement membrane; collagen; cytokine; mutagenesis; recombinant production;
D O I
10.1046/j.1432-1327.1998.2550060.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
A surface plasmon resonance assay was used to analyze the binding of platelet-derived growth factor (PDGF)-AA and PDGF-BB to various proteins of the extracellular matrix. This identified several collagen types; laminin-l, nidogen, perlecan and BM-40 as potential ligands for PDGF with K-d values in the range 2-3200 nM. Perlecan and BM-40 were used to examine the domain specificity and other parameters of the interactions. Recombinant human and mouse BM-40 were shown to bind both PDGFs in a similar manner with a K-d of about 5-10 nM. Studies with deletion mutants of human BM-40 demonstrated binding to its C-terminal extracellular calcium-binding (EC) module, yet the interaction did not require calcium. This distinguishes this from the binding of the EC module to various collagen types, which is strictly calcium dependent. Furthermore, deletion of helix alpha C or two point mutations in helix alpha A of the EC module either enhanced or abolished binding to collagen IV. Since these mutations had no effects on binding to PDGF it demonstrated the presence of two different binding epitopes. Binding of PDGF-BB to the perlecan core protein could be mapped to its domain III-2 (K-d = 8 nM) with lower affinities shown for domains I, IV-1 and V (K-d = 34-64 nM). Other perlecan domains (II, III-1, III-3, IV-2) were inactive. PDGF-AA was also shown to bind domain III-2 but not III-1. Neither nidogen, BM-40 or perlecan domain III-2 interfered with the binding of PDGF to its alpha and beta receptors, however, suggesting that these interactions may be mainly used for storage of PDGF in the extracellular matrix.
引用
收藏
页码:60 / 66
页数:7
相关论文
共 46 条
[1]   NH2-TERMINAL EXTENSIONS ON SKIN COLLAGEN FROM SHEEP WITH A GENETIC DEFECT IN CONVERSION OF PROCOLLAGEN INTO COLLAGEN [J].
BECKER, U ;
TIMPL, R ;
HELLE, O ;
PROCKOP, DJ .
BIOCHEMISTRY, 1976, 15 (13) :2853-2862
[2]   The C-terminal domain V of perlecan promotes beta 1 integrin-mediated cell adhesion, binds heparin, nidogen and fibulin-2 and can be modified by glycosaminoglycans [J].
Brown, JC ;
Sasaki, T ;
Gohring, W ;
Yamada, Y ;
Timpl, R .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1997, 250 (01) :39-46
[3]   2 PDGF-B CHAIN RESIDUES, ARGININE-27 AND ISOLEUCINE-30, MEDIATE RECEPTOR-BINDING AND ACTIVATION [J].
CLEMENTS, JM ;
BAWDEN, LJ ;
BLOXIDGE, RE ;
CATLIN, G ;
COOK, AL ;
CRAIG, S ;
DRUMMOND, AH ;
EDWARDS, RM ;
FALLON, A ;
GREEN, DR ;
HELLEWELL, PG ;
KIRWIN, PM ;
NAYEE, PD ;
RICHARDSON, SJ ;
BROWN, D ;
CHAHWALA, SB ;
SNAREY, M ;
WINSLOW, D .
EMBO JOURNAL, 1991, 10 (13) :4113-4120
[4]   Structural characterization of recombinant domain II of the basement membrane proteoglycan perlecan [J].
Costell, M ;
Sasaki, T ;
Mann, K ;
Yamada, Y ;
Timpl, R .
FEBS LETTERS, 1996, 396 (2-3) :127-131
[5]   Characterization of recombinant perlecan domain I and its substitution by glycosaminoglycans and oligosaccharides [J].
Costell, M ;
Mann, K ;
Yamada, Y ;
Timpl, R .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1997, 243 (1-2) :115-121
[6]   BIOSPECIFIC INTERACTION ANALYSIS USING SURFACE-PLASMON RESONANCE DETECTION APPLIED TO KINETIC, BINDING-SITE AND CONCENTRATION ANALYSIS [J].
FAGERSTAM, LG ;
FROSTELLKARLSSON, A ;
KARLSSON, R ;
PERSSON, B ;
RONNBERG, I .
JOURNAL OF CHROMATOGRAPHY, 1992, 597 (1-2) :397-410
[7]   THE EXTRACELLULAR REGULATION OF GROWTH-FACTOR ACTION [J].
FLAUMENHAFT, R ;
RIFKIN, DB .
MOLECULAR BIOLOGY OF THE CELL, 1992, 3 (10) :1057-1065
[8]   RECOMBINANT NIDOGEN CONSISTS OF 3 GLOBULAR DOMAINS AND MEDIATES BINDING OF LAMININ TO COLLAGEN TYPE-IV [J].
FOX, JW ;
MAYER, U ;
NISCHT, R ;
AUMAILLEY, M ;
REINHARDT, D ;
WIEDEMANN, H ;
MANN, K ;
TIMPL, R ;
KRIEG, T ;
ENGEL, J ;
CHU, ML .
EMBO JOURNAL, 1991, 10 (11) :3137-3146
[9]   BINDING OF DIFFERENT DIMERIC FORMS OF PDGF TO HUMAN-FIBROBLASTS - EVIDENCE FOR 2 SEPARATE RECEPTOR TYPES [J].
HELDIN, CH ;
BACKSTROM, G ;
OSTMAN, A ;
HAMMACHER, A ;
RONNSTRAND, L ;
RUBIN, K ;
NISTER, M ;
WESTERMARK, B .
EMBO JOURNAL, 1988, 7 (05) :1387-1393
[10]  
Heldin CH., 1996, MOL CELLULAR BIOL WO, P249