THERMAL-STABILITY AND FOLDING OF THE COLLAGEN TRIPLE HELIX AND THE EFFECTS OF MUTATIONS IN OSTEOGENESIS IMPERFECTA ON THE TRIPLE HELIX OF TYPE-I COLLAGEN

被引:106
作者
BACHINGER, HP [1 ]
MORRIS, NP [1 ]
DAVIS, JM [1 ]
机构
[1] OREGON HLTH SCI UNIV,DEPT BIOCHEM & MOLEC BIOL,PORTLAND,OR 97201
来源
AMERICAN JOURNAL OF MEDICAL GENETICS | 1993年 / 45卷 / 02期
关键词
COLLAGEN; THERMAL STABILITY; FOLDING; OSTEOGENESIS IMPERFECTA; PPIASE;
D O I
10.1002/ajmg.1320450204
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Osteogenesis imperfecta (OI) is an inherited disease in which 90% of the cases result from mutations in the 2 genes, proalpha1 and proalpha2, coding for type I collagen. Type I collagen is a trimeric molecule, (alpha1)2alpha2, which is dominated both structurally and functionally by the 300 nm triple-helical domain. Most 01 mutations occur in this domain and almost all point mutations result in the substitution of other amino acids for the obligate glycine which occurs at every third residue. The phenotypic effects of these mutations are frequently attributed in part to alterations in the stability and rate of folding of the triple helix. In order to better understand the relationship between glycine substitutions and stability we review current concepts of the forces governing triple helical stability, denaturational and predenaturational unfolding, and the techniques of measuring stability. From observations on the stability of several collagen types as well as synthetic tripeptides, we present a model for stability based on the contribution of individual and neighboring tripeptide units to the local stability. Although in preliminary form, this empirical model can account for the observed shifts in the T(m) of many of the point mutations described. The folding of the triple helix is reviewed. The involvement of peptidyl prolyl cis-trans isomerase in this process in vivo is demonstrated by the inhibition of collagen folding in fibroblasts by cyclosporin A. An hypothesis based on the relationship between the thermal stability at the site of mutation and the propensity for renucleation of folding is proposed.
引用
收藏
页码:152 / 162
页数:11
相关论文
共 70 条
  • [1] SEQUENCE SPECIFIC THERMAL-STABILITY OF THE COLLAGEN TRIPLE HELIX
    BACHINGER, HP
    DAVIS, JM
    [J]. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 1991, 13 (03) : 152 - 156
  • [2] BACHINGER HP, 1987, J BIOL CHEM, V262, P17144
  • [3] FOLDING MECHANISM OF THE TRIPLE HELIX IN TYPE-III COLAGEN AND TYPE-III PN-COLLAGEN - ROLE OF DISULFIDE BRIDGES AND PEPTIDE-BOND ISOMERIZATION
    BACHINGER, HP
    BRUCKNER, P
    TIMPL, R
    PROCKOP, DJ
    ENGEL, J
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1980, 106 (02): : 619 - 632
  • [4] BACHINGER HP, 1990, MATRIX, V10, P331
  • [5] ROLE OF CIS-TRANS ISOMERIZATION OF PEPTIDE-BONDS IN COIL REVERSIBLE TRIPLE HELIX CONVERSION OF COLLAGEN
    BACHINGER, HP
    BRUCKNER, P
    TIMPL, R
    ENGEL, J
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1978, 90 (03): : 605 - 613
  • [6] BACHINGER HP, 1989, CYTOSKELETAL EXTRACE, P171
  • [7] CHANGES IN COLLAGEN STABILITY AND FOLDING IN LETHAL PERINATAL OSTEOGENESIS IMPERFECTA - THE EFFECT OF ALPHA-1(I)-CHAIN GLYCINE-TO-ARGININE SUBSTITUTIONS
    BAKER, AT
    RAMSHAW, JAM
    CHAN, D
    COLE, WG
    BATEMAN, JF
    [J]. BIOCHEMICAL JOURNAL, 1989, 261 (01) : 253 - 257
  • [8] STRUCTURE OF CDNA CLONES CODING FOR HUMAN TYPE-II PROCOLLAGEN - THE ALPHA-1(II) CHAIN IS MORE SIMILAR TO THE ALPHA-1(I) CHAIN THAN 2 OTHER ALPHA-CHAINS OF FIBRILLAR COLLAGENS
    BALDWIN, CT
    REGINATO, AM
    SMITH, C
    JIMENEZ, SA
    PROCKOP, DJ
    [J]. BIOCHEMICAL JOURNAL, 1989, 262 (02) : 521 - 528
  • [9] BATEMAN JF, 1988, J BIOL CHEM, V263, P11627
  • [10] BATEMAN JF, 1990, 4TH INT C OST IMP