Berjanskii M V, Riley M I, Xie A, Semenchenko V, Folk W R, Van Doren S R
Department of Biochemistry, University of Missouri, Columbia, Missouri 65211, USA.
J Biol Chem. 2000 Nov 17;275(46):36094-103. doi: 10.1074/jbc.M006572200.
The NMR structure of the N-terminal, DnaJ-like domain of murine polyomavirus tumor antigens (PyJ) has been determined to high precision, with root mean square deviations to the mean structure of 0.38 A for backbone atoms and 0.94 A for all heavy atoms of ordered residues 5-41 and 50-69. PyJ possesses a three-helix fold, in which anti-parallel helices II and III are bridged by helix I, similar to the four-helix fold of the J domains of DnaJ and human DnaJ-1. PyJ differs significantly in the lengths of N terminus, helix I, and helix III. The universally conserved HPD motif appears to form a His-Pro C-cap of helix II. Helix I features a stabilizing Schellman C-cap that is probably conserved universally among J domains. On the helix II surface where positive charges of other J domains have been implicated in binding of hsp70s, PyJ contains glutamine residues. Nonetheless, chimeras that replace the J domain of DnaJ with PyJ function like wild-type DnaJ in promoting growth of Escherichia coli. This activity can be modulated by mutations of at least one of these glutamines. T antigen mutations reported to impair cellular transformation by the virus, presumably via interactions with PP2A, cluster in the hydrophobic folding core and at the extreme N terminus, remote from the HPD loop.
小鼠多瘤病毒肿瘤抗原（PyJ）N 端类似 DnaJ 结构域的核磁共振结构已被高精度测定，对于有序残基 5 - 41 和 50 - 69 的主链原子，相对于平均结构的均方根偏差为 0.38 Å，所有重原子的均方根偏差为 0.94 Å。PyJ 具有三螺旋折叠结构，其中反平行的螺旋 II 和螺旋 III 由螺旋 I 桥接，类似于 DnaJ 和人 DnaJ - 1 的 J 结构域的四螺旋折叠。PyJ 在 N 端、螺旋 I 和螺旋 III 的长度上有显著差异。普遍保守的 HPD 基序似乎形成了螺旋 II 的组氨酸 - 脯氨酸 C 帽。螺旋 I 具有一个稳定的 Schellman C 帽，可能在 J 结构域中普遍保守。在其他 J 结构域的正电荷与 hsp70 结合有关的螺旋 II 表面，PyJ 含有谷氨酰胺残基。尽管如此，用 PyJ 取代 DnaJ 的 J 结构域的嵌合体在促进大肠杆菌生长方面的功能与野生型 DnaJ 相似。这种活性可以通过这些谷氨酰胺中至少一个的突变来调节。据报道，T 抗原突变会损害病毒的细胞转化，大概是通过与 PP2A 的相互作用，这些突变聚集在疏水折叠核心和极端 N 端，远离 HPD 环。
