Kiselyov Vladislav V, Bock Elisabeth, Berezin Vladimir, Poulsen Flemming M
Protein Laboratory, Institute of Molecular Pathology, Copenhagen DK-2200, Denmark.
Protein Sci. 2006 Jun;15(6):1512-5. doi: 10.1110/ps.062207906.
Fibroblast growth factor (FGF) receptors (FGFRs) regulate a multitude of cellular processes during embryogenesis and in the adult. The extracellular part of the prototypical FGFR consists of three Ig modules (Ig1 - Ig3), in which Ig2 and Ig3 determine affinity and specificity for FGF and heparin, while the Ig1 module is thought to have a regulatory function. The crystal structures of the Ig2 and Ig3 modules alone and in complex with FGF have previously been reported. The structure of the Ig1 module is unknown, and very little is known about the structural determinants for the regulatory function of this module. We describe here the NMR structure of the Ig1 module of mouse FGFR1. The three-dimensional fold of the module belongs to the intermediate Ig subgroup and can be described as a beta-barrel consisting of two beta-sheets. One sheet is formed by A', G, F, C, and C', and the other by A, B, B', E, and D beta-strands. The overall strand topology of the Ig1 module is similar to that of the Ig2 and Ig3 modules. However, the A/A' loop of the Ig1 module is much longer than that of the Ig2 and Ig3 modules. It contains eight extra residues compared to the Ig3 module, and five extra residues compared to Ig2.
成纤维细胞生长因子（FGF）受体（FGFRs）在胚胎发育和成年期调节多种细胞过程。典型FGFR的细胞外部分由三个免疫球蛋白模块（Ig1 - Ig3）组成，其中Ig2和Ig3决定对FGF和肝素的亲和力和特异性，而Ig1模块被认为具有调节功能。此前已报道了单独的Ig2和Ig3模块以及与FGF结合的复合物的晶体结构。Ig1模块的结构未知，关于该模块调节功能的结构决定因素也知之甚少。我们在此描述小鼠FGFR1的Ig1模块的核磁共振结构。该模块的三维折叠属于中间Ig亚组，可描述为由两个β-折叠片组成的β-桶。一个折叠片由A'、G、F、C和C'链组成，另一个由A、B、B'、E和Dβ-链组成。Ig1模块的整体链拓扑结构与Ig2和Ig3模块相似。然而，Ig1模块的A/A'环比Ig2和Ig3模块的长得多。与Ig3模块相比，它包含八个额外的残基，与Ig2相比包含五个额外的残基。
