Noda Yukiko, Kohjima Motoyuki, Izaki Tomoko, Ota Kazuhisa, Yoshinaga Sosuke, Inagaki Fuyuhiko, Ito Takashi, Sumimoto Hideki
Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
J Biol Chem. 2003 Oct 31;278(44):43516-24. doi: 10.1074/jbc.M306330200. Epub 2003 Aug 14.
The PB1 (Phox and Bem 1) domain is a recently identified module that mediates formation of a heterodimeric complex with other PB1 domain, e.g. the complexes between the phagocyte oxidase activators p67phox and p40phox and between the yeast polarity proteins Bem1p and Cdc24p. These PB1 domains harbor either a conserved lysine residue on one side or an acidic OPCA (OPR/PC/AID) motif around the other side; the lysine of p67phox or Bem1p likely binds to the OPCA of p40phox or Cdc24p, respectively, via electrostatic interactions. To further understand molecular recognition by PB1 domains, here we investigate the interactions mediated by proteins presenting both the lysine and OPCA on a single PB1 domain, namely Par6, atypical protein kinase C (aPKC), and ZIP. Par6 and aPKC form a complex via the interaction of the Par6 lysine with aPKC-OPCA but not via that between the aPKC lysine and Par6-OPCA, thereby localizing to the tight junction of epithelial cells. aPKC also uses its OPCA to interact with ZIP, another protein that has a PB1 domain presenting both the lysine and OPCA, whereas aPKC binds via the conserved lysine to MEK5 in the same manner as ZIP interacts with MEK5. In addition, ZIP can form a homotypic complex via the conserved electrostatic interactions. Thus the PB1 domain appears to be a protein module that fully exploits its two mutually interacting elements in molecular recognition to expand its repertoire of protein-protein interactions.
PB1（Phox和Bem 1）结构域是最近发现的一个模块，它介导与其他PB1结构域形成异二聚体复合物，例如吞噬细胞氧化酶激活剂p67phox和p40phox之间以及酵母极性蛋白Bem1p和Cdc24p之间的复合物。这些PB1结构域一侧带有保守的赖氨酸残基，另一侧带有酸性OPCA（OPR/PC/AID）基序；p67phox或Bem1p的赖氨酸可能分别通过静电相互作用与p40phox或Cdc24p的OPCA结合。为了进一步了解PB1结构域的分子识别机制，我们在此研究了由单个PB1结构域同时呈现赖氨酸和OPCA的蛋白质介导的相互作用，即Par6、非典型蛋白激酶C（aPKC）和ZIP。Par6和aPKC通过Par6赖氨酸与aPKC-OPCA的相互作用形成复合物，而不是通过aPKC赖氨酸与Par6-OPCA之间的相互作用，从而定位于上皮细胞的紧密连接处。aPKC还利用其OPCA与ZIP相互作用，ZIP是另一种具有同时呈现赖氨酸和OPCA的PB1结构域的蛋白质，而aPKC通过保守的赖氨酸与MEK5结合，其方式与ZIP与MEK5相互作用相同。此外，ZIP可以通过保守的静电相互作用形成同型复合物。因此，PB1结构域似乎是一个蛋白质模块，它在分子识别中充分利用其两个相互作用的元件来扩展其蛋白质-蛋白质相互作用的种类。
