PURIFICATION OF COMPONENT-A OF RAB GERANYLGERANYL TRANSFERASE - POSSIBLE IDENTITY WITH THE CHOROIDEREMIA GENE-PRODUCT
PURIFICATION OF COMPONENT-A OF RAB GERANYLGERANYL TRANSFERASE - POSSIBLE IDENTITY WITH THE CHOROIDEREMIA GENE-PRODUCT
复制标题
DOI：
10.1016/0092-8674(92)90253-9
复制
发表时间：
1992-09-18
期刊：
影响因子：
64.5
通讯作者：
GOLDSTEIN, JL
中科院分区：
文献类型：
--
作者：
SEABRA, MC;BROWN, MS;GOLDSTEIN, JL
来自大鼠脑的Rab香叶基香叶基转移酶(GG转移酶)含有两种成分，A和B。成分B包含60和38kd的多肽。在这里，我们报告了组分 A（单一 95 kd 多肽）的纯化。该全酶将 H-3-香叶基-香叶基连接到两个 GTP 结合蛋白 Rab3A 和 Rab1A 中的半胱氨酸上。当 Rab1A COOH 末端 CysCys 序列中的两个半胱氨酸突变为丝氨酸时，该反应被取消。该突变蛋白抑制 H-3-香叶基香叶基向野生型 Rab1A 和 Rab3A 的转移，表明该酶识别与 COOH 末端不同的保守序列。来自大鼠成分 A 的六种肽与无脉络膜血症（一种 X 连锁视网膜变性疾病）中缺陷基因的产物显示出惊人的相似性。无脉络膜蛋白类似于与 Rab3A 结合的 Rab3A GDI。我们假设组分 A 结合 Rab 中的保守序列，组分 B 转移香叶基香叶基。该反应的缺陷可能会导致无脉络膜血症。
Rab geranylgeranyl transferase (GG transferase) from rat brain contains two components, A and B. Component B comprises polypeptides of 60 and 38 kd. Here we report the purification of component A, a single 95 kd polypeptide. The holoenzyme attaches H-3-geranyl-geranyl to cysteines in two GTP-binding proteins, Rab3A and Rab1A. The reaction is abolished when both cysteines in the COOH-terminal CysCys sequence of Rab1A are mutated to serines. The mutant protein inhibits transfer of H-3-geranylgeranyl to wild-type Rab1A and Rab3A, suggesting that the enzyme recognizes conserved sequences distinct from the COOH-terminus. Six peptides from rat component A show striking similarity to the product of the defective gene in choroideremia, an X-linked retinal degeneration disease. The choroideremia protein resembles Rab3A GDI, which binds Rab3A. We hypothesize that component A binds conserved sequences in Rab and that component B transfers geranylgeranyl. A defect in this reaction may cause choroideremia.