BiP binds type I procollagen pro alpha chains with mutations in the carboxyl-terminal propeptide synthesized by cells from patients with osteogenesis imperfecta.
BiP binds type I procollagen pro alpha chains with mutations in the carboxyl-terminal propeptide synthesized by cells from patients with osteogenesis imperfecta.
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DOI：
10.1016/s0021-9258(17)46834-7
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发表时间：
1993-08
期刊：
影响因子：
--
通讯作者：
Steven D Chessler;P. H. Byers
中科院分区：
文献类型：
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作者：
Steven D Chessler;P. H. Byers
成骨不全症 (OI) 是一种由 I 型原胶原编码基因突变引起的疾病，在 20 个来自成骨不全症 (OI) 患者的成纤维细胞株中，有 3 个成纤维细胞株 BiP (GRP78) 的合成增加，BiP (GRP78) 是一种与 hsp70 相关的内质网驻留蛋白。所有三种菌株的原 α1(I) 链都携带独特的突变，会损害 I 型原胶原链的缔合。免疫沉淀和脉冲追踪实验表明，BiP（免疫球蛋白重链结合蛋白）在短暂滞后后稳定结合这三种细胞株中的前 α1(I) 链。抗坏血酸可以增加原胶原合成，增加这三种菌株中的 BiP 合成和含量，而其他菌株则不会。在这三种菌株之一中，BiP 含量在抗坏血酸处理之前持续升高，并且 BiP 的诱导性较差。该菌株还具有相对较高水平的GRP94（另一种内质网驻留应激蛋白）的合成和含量。对三种细胞株进行预处理以增加其 BiP 含量，可减少随后的抗坏血酸介导的 BiP 诱导。所检查的其他 17 种 OI 菌株中的 BiP 合成正常，这些菌株具有多种 I 型前胶原突变。这些结果表明，BiP 是由具有特定类型突变的前胶原诱导并结合的：羧基末端前肽中的突变会干扰链缔合。 BiP 对 OI 细胞株中此类前胶原的识别表明，BiP 在对某些引起疾病的异常蛋白产生的生理反应中发挥作用。
Of 20 fibroblast cell strains from patients with osteogenesis imperfecta (OI), a disease caused by mutations in the genes encoding type I procollagen, three had increased synthesis of BiP (GRP78), an hsp70-related, endoplasmic reticulum-resident protein. All three strains carry unique mutations in pro alpha 1(I) chains which impair type I procollagen chain association. Immunoprecipitation and pulse-chase experiments show that BiP (immunoglobulin heavy chain-binding protein) stably binds pro alpha 1(I) chains in these three cell strains after a brief lag. Ascorbate, which increases procollagen synthesis, increases BiP synthesis and content in these three strains and not in the others. In one of these three strains, BiP content is constitutively elevated prior to ascorbate treatment, and BiP is less inducible. This strain also has relatively high levels of synthesis and content of GRP94, another endoplasmic reticulum-resident stress protein. Pretreating each of the three cell strains to increase their BiP content reduces subsequent ascorbate-mediated BiP induction. BiP synthesis in the 17 other OI strains examined, which had a variety of type I procollagen mutations, was normal. These results suggest that BiP is induced by and binds procollagen with specific types of mutations: ones in the carboxyl-terminal propeptide that interfere with chain association. The recognition by BiP of such procollagen in OI cell strains shows that BiP plays a role in the physiological response to the production of some disease-producing abnormal proteins.