Specific recognition of the collagen triple helix by chaperone HSP47 II. The HSP47-binding structural motif in collagens and related proteins
Specific recognition of the collagen triple helix by chaperone HSP47 II. The HSP47-binding structural motif in collagens and related proteins
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DOI：
10.1074/jbc.m601369200
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发表时间：
2006-04-21
影响因子：
4.8
通讯作者：
Kitagawa, K
中科院分区：
文献类型：
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作者：
Koide, T;Nishikawa, Y;Kitagawa, K
内质网伴侣热休克蛋白47（HSP 47）在前胶原的生物合成中起着重要作用。HSP 47的功能依赖于其与正确折叠的三螺旋区域的特异性相互作用，该三螺旋区域由Gly-Xaa-Yaa重复序列组成，并且已经显示Yaa位置上的Arg残基对于这种相互作用是重要的。含有关键Arg（定义为Arg（0））的N-末端邻接三联体中Yaa位置（Yaa（-3））处的氨基酸也被认为直接被HSP 47识别（Koide，T.，Asada，S.，Takahara，Y.，Nishikawa，Y.，永田，K.，和Kitagawa，K.（2006）J.Biol.Chem.281，3432 - 3438）。基于这一发现，我们使用合成的胶原肽研究了Yaa（-3）结构与HSP 47结合之间的关系。所得结果表明Yaa（-3）的结构决定了与HSP 47的结合亲和力。当Yaa（-3）为Thr时，观察到最大结合。此外，通过利用异源三聚体胶原蛋白模型肽分析了三螺旋中这些关键残基所需的相对空间排列，每个模型肽含有一个Thr（-3）和一个Arg（0）。结果表明，HSP 47仅识别Yaa（-3）和Arg（0）残基，当它们在同一肽链上时。总之，所获得的数据使我们确定了胶原蛋白三螺旋中的HSP 47结合结构表位，并确定了一级结构中的HSP 47结合基序。对人类蛋白质数据库的模体搜索预测了这种分子伴侣的候选客户。检索结果表明，并非所有的胶原蛋白家族蛋白都需要HSP 47的陪伴。
The endoplasmic reticulum-resident chaperone heat-shock protein 47 (HSP47) plays an essential role in procollagen biosynthesis. The function of HSP47 relies on its specific interaction with correctly folded triple-helical regions comprised of Gly-Xaa-Yaa repeats, and Arg residues at Yaa positions have been shown to be important for this interaction. The amino acid at the Yaa position (Yaa(-3)) in the N-terminal-adjoining triplet containing the critical Arg ( defined as Arg(0)) was also suggested to be directly recognized by HSP47 (Koide, T., Asada, S., Takahara, Y., Nishikawa, Y., Nagata, K., and Kitagawa, K. ( 2006) J. Biol. Chem. 281, 3432 - 3438). Based on this finding, we examined the relationship between the structure of Yaa(-3) and HSP47 binding using synthetic collagenous peptides. The results obtained indicated that the structure of Yaa(-3) determined the binding affinity for HSP47. Maximal binding was observed when Yaa(-3) was Thr. Moreover, the required relative spatial arrangement of these key residues in the triple helix was analyzed by taking advantage of heterotrimeric collagen-model peptides, each of which contains one Thr(-3) and one Arg(0). The results revealed that HSP47 recognizes the Yaa(-3) and Arg(0) residues only when they are on the same peptide strand. Taken together, the data obtained led us to define the HSP47-binding structural epitope in the collagen triple helix and also define the HSP47-binding motif in the primary structure. A motif search against human protein database predicted candidate clients for this molecular chaperone. The search result indicated that not all collagen family proteins require the chaperoning by HSP47.