The School of Molecular and Biomedical Science, The University of Adelaide Adelaide, SA, Australia.
Front Endocrinol (Lausanne). 2012 Mar 2;3:38. doi: 10.3389/fendo.2012.00038. eCollection 2012.
Insulin-like growth factor binding proteins (IGFBP-1 to -6) bind insulin-like growth factors-I and -II (IGF-I and IGF-II) with high affinity. These binding proteins maintain IGFs in the circulation and direct them to target tissues, where they promote cell growth, proliferation, differentiation, and survival via the type 1 IGF receptor. IGFBPs also interact with many other molecules, which not only influence their modulation of IGF action but also mediate IGF-independent activities that regulate processes such as cell migration and apoptosis by modulating gene transcription. IGFBPs-1 to -6 are structurally similar proteins consisting of three distinct domains, N-terminal, linker, and C-terminal. There have been major advances in our understanding of IGFBP structure in the last decade and a half. While there is still no structure of an intact IGFBP, several structures of individual N- and C-domains have been solved. The structure of a complex of N-BP-4:IGF-I:C-BP-4 has also been solved, providing a detailed picture of the structural features of the IGF binding site and the mechanism of binding. Structural studies have also identified features important for interaction with extracellular matrix components and integrins. This review summarizes structural studies reported so far and highlights features important for binding not only IGF but also other partners. We also highlight future directions in which structural studies will add to our knowledge of the role played by the IGFBP family in normal growth and development, as well as in disease.
胰岛素样生长因子结合蛋白（IGFBP-1 至 -6）以高亲和力结合胰岛素样生长因子-I 和 -II（IGF-I 和 IGF-II）。这些结合蛋白将 IGF 保留在循环中，并将其引导至靶组织，在靶组织中，它们通过 1 型 IGF 受体促进细胞生长、增殖、分化和存活。IGFBPs 还与许多其他分子相互作用，这些分子不仅影响它们对 IGF 作用的调节，而且还通过调节基因转录来调节细胞迁移和细胞凋亡等过程的 IGF 非依赖性活性。IGFBPs-1 至 -6 是结构相似的蛋白质，由三个不同的结构域组成，即 N 端、连接子和 C 端。在过去的十五年中，我们对 IGFBP 结构的理解取得了重大进展。虽然仍然没有完整的 IGFBP 结构，但已经解决了几个单独的 N 和 C 结构域的结构。N-BP-4:IGF-I:C-BP-4 复合物的结构也已解决，提供了 IGF 结合位点的结构特征和结合机制的详细图片。结构研究还确定了与细胞外基质成分和整合素相互作用的重要特征。这篇综述总结了迄今为止报道的结构研究，并强调了不仅与 IGF 结合而且与其他伴侣结合的重要特征。我们还强调了结构研究在未来将如何增加我们对 IGFBP 家族在正常生长发育以及疾病中所起作用的知识。
