Minamino T, Tame J R, Namba K, Macnab R M
Protonic Nanomachine Project ERATO, JST, 3-4 Hikaridai, Seika, Kyoto 619-0237, Japan.
J Mol Biol. 2001 Oct 5;312(5):1027-36. doi: 10.1006/jmbi.2001.5000.
The ATPase FliI of the Salmonella type III flagellar protein export apparatus is a 456 amino acid residue cytoplasmic protein consisting of two regions, an N-terminal flagellum-specific region and a C-terminal ATPase region. It forms a complex with a regulatory protein FliH in the cytoplasm. Multi-angle light-scattering studies indicate that FliH forms a homodimer, (FliH)2, and that FliH and FliI together form a heterotrimer, (FliH)2FliI. Mobility upon gel-filtration chromatography gives much higher apparent molecular masses for both species, whereas the mobility of FliI is normal. Sedimentation velocity measurements indicate that both (FliH)2 and the FliH/FliI complex are quite elongated. We have analyzed FliH, FliI and the FliH/FliI complex for proteolytic sensitivity. FliI was degraded by clostripain into two stable fragments, one of 48 kDa (FliI(CL48), missing the first seven amino acid residues) and the other of 46 kDa (FliI(CL46), missing the first 26 residues). Small amounts of two closely spaced 38 kDa fragments (FliI(CL38), missing the first 93 and 97 residues, respectively) were also detected. The FliH homodimer was insensitive to clostripain proteolysis and provided protection to FliI within the FliH/FliI complex. Neither FliI(CL48) nor FliI(CL46) could form a complex with FliH, demonstrating that the N terminus of FliI is essential for the interaction. ATP, AMP-PNP, and ADP bound forms of FliI within the FliH/FliI complex regained sensitivity to clostripain cleavage. Also, the sensitivity of the two FliI(CL38) cleavage sites was much greater in the ATP and AMP-PNP bound forms than in either the ADP bound form or nucleotide-free FliI. The ATPase domain itself was insensitive to clostripain cleavage. We suggest that the N-terminal flagellum-specific region of FliI is flexible and changes its conformation during the ATP hydrolysis cycle.
沙门氏菌III型鞭毛蛋白输出装置的ATP酶FliI是一种由456个氨基酸残基组成的胞质蛋白,由两个区域组成,一个N端鞭毛特异性区域和一个C端ATP酶区域。它在细胞质中与调节蛋白FliH形成复合物。多角度光散射研究表明,FliH形成同二聚体(FliH)2,并且FliH和FliI一起形成异三聚体(FliH)2FliI。凝胶过滤色谱法中的迁移率显示这两种物质的表观分子量要高得多,而FliI的迁移率正常。沉降速度测量表明,(FliH)2和FliH/FliI复合物都相当细长。我们分析了FliH、FliI和FliH/FliI复合物对蛋白酶解的敏感性。FliI被梭菌蛋白酶降解为两个稳定片段,一个48 kDa(FliI(CL48),缺失前七个氨基酸残基),另一个46 kDa(FliI(CL46),缺失前26个残基)。还检测到少量两个紧密间隔的38 kDa片段(FliI(CL38),分别缺失前93和97个残基)。FliH同二聚体对梭菌蛋白酶解不敏感,并为FliH/FliI复合物中的FliI提供保护。FliI(CL48)和FliI(CL46)都不能与FliH形成复合物,表明FliI的N端对于相互作用至关重要。FliH/FliI复合物中ATP、AMP-PNP和ADP结合形式的FliI恢复了对梭菌蛋白酶切割的敏感性。此外,两种FliI(CL38)切割位点在ATP和AMP-PNP结合形式下的敏感性比在ADP结合形式或无核苷酸的FliI中要高得多。ATP酶结构域本身对梭菌蛋白酶切割不敏感。我们认为,FliI的N端鞭毛特异性区域是灵活的,并且在ATP水解循环中改变其构象。