Paaventhan Palasingam, Joseph Jeremiah S, Seow See Voon, Vaday Shai, Robinson Howard, Chua Kaw Yan, Kolatkar Prasanna R
Genome Institute of Singapore, 117528 Singapore, Singapore.
J Mol Biol. 2003 Sep 12;332(2):461-70. doi: 10.1016/s0022-2836(03)00923-9.
Fve, a major fruiting body protein from Flammulina velutipes, a mushroom possessing immunomodulatory activity, stimulates lymphocyte mitogenesis, suppresses systemic anaphylaxis reactions and edema, enhances transcription of IL-2, IFN-gamma and TNF-alpha, and hemagglutinates red blood cells. It appears to be a lectin with specificity for complex cell-surface carbohydrates. Fve is a non-covalently linked homodimer containing no Cys, His or Met residues. It shares sequence similarity only to the other fungal immunomodulatory proteins (FIPs) LZ-8, Gts, Vvo and Vvl, all of unknown structure. The 1.7A structure of Fve solved by single anomalous diffraction of NaBr-soaked crystals is novel: each monomer consists of an N-terminal alpha-helix followed by a fibronectin III (FNIII) fold. The FNIII fold is the first instance of "pseudo-h-type" topology, a transition between the seven beta-stranded s-type and the eight beta-stranded h-type topologies. The structure suggests that dimerization, critical for the activity of FIPs, occurs by 3-D domain swapping of the N-terminal helices and is stabilized predominantly by hydrophobic interactions. The structure of Fve is the first in this lectin family to be reported, and the first of an FNIII domain-containing protein of fungal origin.
金针菇是一种具有免疫调节活性的蘑菇，Fve是金针菇主要的子实体蛋白，它能刺激淋巴细胞有丝分裂，抑制全身性过敏反应和水肿，增强白细胞介素-2、γ-干扰素和肿瘤坏死因子-α的转录，并能使红细胞发生凝集。它似乎是一种对复杂细胞表面碳水化合物具有特异性的凝集素。Fve是一种非共价连接的同型二聚体，不含半胱氨酸、组氨酸或甲硫氨酸残基。它仅与其他结构未知的真菌免疫调节蛋白（FIPs）LZ-8、Gts、Vvo和Vvl具有序列相似性。通过NaBr浸泡晶体的单异常衍射解析得到的Fve的1.7埃结构是新颖的：每个单体由一个N端α螺旋和一个纤连蛋白III（FNIII）折叠组成。FNIII折叠是“假h型”拓扑结构的首个实例，是七股β链s型和八股β链h型拓扑结构之间的过渡。该结构表明，对FIPs活性至关重要的二聚化是通过N端螺旋的三维结构域交换发生的，并且主要通过疏水相互作用得以稳定。Fve的结构是该凝集素家族中首个被报道的，也是首个源自真菌的含FNIII结构域蛋白的结构。
