Tremmel Dirk, Tropschug Maximilian
Institut für Biochemie und Molekularbiologie, Zentrum für Biochemie und molekulare Zellforschung, Albert-Ludwigs-Universität Freiburg, Hermann-Herder-Strasse 7, D-79104 Freiburg, Germany.
J Mol Biol. 2007 May 25;369(1):55-68. doi: 10.1016/j.jmb.2007.01.092. Epub 2007 Mar 12.
FK506 binding proteins (FKBPs) belong to the family of peptidyl prolyl cis-trans isomerases (PPIases) catalyzing the cis/trans isomerisation of Xaa-Pro bonds in oligopeptides and proteins. FKBPs are involved in folding, assembly and trafficking of proteins. However, only limited knowledge is available about the roles of FKBPs in the endoplasmic reticulum (ER) and their interaction with other proteins. Here we show the ER located Neurospora crassa FKBP22 to be a dimeric protein with PPIase and a novel chaperone activity. While the homodimerization of FKBP22 is mediated by its carboxy-terminal domain, the amino-terminal domain is a functional FKBP domain. The chaperone activity is mediated by the FKBP domain but is exhibited only by the full-length protein. We further demonstrate a direct interaction between FKBP22 and BiP, the major Hsp70 chaperone in the ER. The binding to BiP is mediated by the FKBP domain of FKBP22. Interestingly BiP enhances the chaperone activity of FKBP22. Both proteins form a stable complex with an unfolded substrate protein and thereby prevent its aggregation. These results suggest that BiP and FKBP22 form a folding helper complex with a high chaperoning capacity in the ER of Neurospora crassa.
FK506结合蛋白（FKBPs）属于肽基脯氨酰顺反异构酶（PPIases）家族，可催化寡肽和蛋白质中Xaa-Pro键的顺/反异构化。FKBPs参与蛋白质的折叠、组装和运输。然而，关于FKBPs在内质网（ER）中的作用及其与其他蛋白质的相互作用，目前了解有限。在此，我们展示了位于内质网的粗糙脉孢菌FKBP22是一种具有PPIase和新型伴侣活性的二聚体蛋白。虽然FKBP22的同二聚化由其羧基末端结构域介导，但氨基末端结构域是一个功能性的FKBP结构域。伴侣活性由FKBP结构域介导，但仅由全长蛋白表现出来。我们进一步证明了FKBP22与内质网中主要的Hsp70伴侣BiP之间存在直接相互作用。与BiP的结合由FKBP22的FKBP结构域介导。有趣的是，BiP增强了FKBP22的伴侣活性。这两种蛋白与未折叠的底物蛋白形成稳定的复合物，从而防止其聚集。这些结果表明，BiP和FKBP22在粗糙脉孢菌的内质网中形成了一个具有高伴侣能力的折叠辅助复合物。
