基质细胞衍生因子-1α（SDF-1α）N端反向肽类似物中意外激动剂活性的结构决定因素。

Structural determinants of unexpected agonist activity in a retro-peptide analogue of the SDF-1alpha N-terminus.

作者信息

Palladino Pasquale, Tizzano Barbara, Pedone Carlo, Ragone Raffaele, Rossi Filomena, Saviano Gabriella, Tancredi Teodorico, Benedetti Ettore

机构信息

Dipartimento delle Scienze Biologiche, CIRPeB, Università Federico II di Napoli, CNR, Italy.

出版信息

FEBS Lett. 2005 Oct 10;579(24):5293-8. doi: 10.1016/j.febslet.2005.07.100.

DOI:10.1016/j.febslet.2005.07.100

PMID:16182292

Abstract

We have synthesised two retro-peptide analogues of the stromal cell derived growth factor 1 (SDF-1alpha) segment known to be critical for CXCR4 receptor binding, corresponding to the sequences HSEFFRCPCRFFESH and HSEFFRGGGRFFESH. We have assayed the ability of these peptides to activate extracellular signal-regulated kinase 1/2 phosphorylation in cells over expressing the SDF-1alpha receptor, finding that the first variant was able to serve as an agonist of CXCR4, whereas the second one was inactive. Finally, by comparing representative solution structures of the two peptides, we have found that the biological response of HSEFFRCPCRFFESH may be ascribed to a beta-beta-type turn motif centred on Phe(4)-Phe(5).

摘要

我们合成了基质细胞衍生生长因子1（SDF-1α）片段的两种反向肽类似物，已知该片段对CXCR4受体结合至关重要，其对应序列为HSEFFRCPCRFFESH和HSEFFRGGGRFFESH。我们检测了这些肽在过表达SDF-1α受体的细胞中激活细胞外信号调节激酶1/2磷酸化的能力，发现第一个变体能够作为CXCR4的激动剂，而第二个则无活性。最后，通过比较这两种肽的代表性溶液结构，我们发现HSEFFRCPCRFFESH的生物学反应可能归因于以Phe(4)-Phe(5)为中心的β-β型转角基序。