COMPETITION FOR BINDING TO INSULIN-LIKE GROWTH-FACTOR (IGF) BINDING PROTEIN-2, 3, 4, AND 5 BY THE IGFS AND IGF ANALOGS
COMPETITION FOR BINDING TO INSULIN-LIKE GROWTH-FACTOR (IGF) BINDING PROTEIN-2, 3, 4, AND 5 BY THE IGFS AND IGF ANALOGS
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DOI：
10.1210/en.131.2.890
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发表时间：
1992-08-01
期刊：
影响因子：
4.8
通讯作者：
CASCIERI, MA
中科院分区：
文献类型：
--
作者：
CLEMMONS, DR;DEHOFF, ML;CASCIERI, MA
胰岛素样生长因子（IGF）I和II以高亲和力与IGF结合蛋白（BP）结合。仅对IGFBP-1和IGFBP-3定义了每种IGF对单个BP的亲和力以及这种高亲和力结合所需的IGF-I分子区域。本研究已经确定了几种IGF类似物（使用体外诱变制备）对纯IGFBP-2、3、4和5的亲和力。结果显示IGFBP-2以类似于IGFBP-1的方式结合这些类似物。例如，A链区（位置49、50、51）或B链（位置3、4）中的突变导致对IGFBP-1或2的亲和力降低大于20倍。相反，A链区的突变对IGFBP-3结合的影响最小，而B链3、4、15、16位的取代使IGF-I亲和力降低至少50倍。在pH 7.4下，与IGFBP-1、2和3相比，类似物与IGFBP-4的结合受B链3、4位置处的取代的影响较小，但IGFBP-4对含有A链取代的类似物的亲和力与IGFBP-1和2类似地大大降低。与IGFBP-5的结合被A或B链取代大大降低，并且大多数突变导致亲和力降低超过100倍。酸性pH 6.0与IGFBP-4对含A链突变体的亲和力增加相关。结果表明，只有IGFBP-1和2对这些类似物中的每一个具有几乎相同的亲和力，而IGFBP-3、4和5具有相似性和显著差异。研究结果表明，不同的结合蛋白具有不同的结构要求，以实现最佳的IGF-I结合。
The insulin-like growth factors (IGF) I and II bind to IGF binding proteins (BP) with high affinity. The affinity of each of the IGFs for individual BPs and the regions of the IGF-I molecule that are required for this high affinity binding have been defined only for IGFBP-1 and IGFBP-3. The present studies have determined the affinity of several IGF analogs (prepared using in vitro mutagenesis) for pure IGFBP-2, 3, 4, and 5. The results show IGFBP-2 binds these analogs in a manner similar to IGFBP-1. For example, a mutation in the A chain region (positions 49, 50, 51) or B chain (positions 3, 4) results in greater than 20-fold reduction in affinity for either IGFBP-1 or 2. In contrast, mutations in the A chain region have minimal effect on binding to IGFBP-3, whereas substitutions at the 3, 4, 15, 16 positions of the B chain reduce IGF-I affinity by at least 50-fold. At pH 7.4, binding of the analogs to IGFBP-4 is less affected by substitutions at the B chain 3, 4 positions compared to IGFBP-1, 2, and 3, but IGFBP-4 affinity for analogs containing the A chain substitutions is greatly reduced similarly to IGFBP-1 and 2. Binding to IGFBP-5 is greatly reduced by either A or B chain substitutions and most of the mutations result in greater than 100-fold reduction in affinity. Acidic pH 6.0 was associated with increased affinity of IGFBP-4 for the A chain containing mutants. The results indicate that only IGFBP-1 and 2 have nearly identical affinity for each of these analogs, whereas IGFBP-3, 4, and 5 have similarities and significant differences. The findings suggest that different binding proteins have differential structural requirements for optimal IGF-I binding.