VCP/p97, an enzyme critical to proteostasis, is regulated through interactions with protein adaptors targeting it to specific cellular tasks. One such adaptor, p47, forms a complex with p97 to direct lipid membrane remodeling. Here, we use NMR and other biophysical methods to study the structural dynamics of p47 and p47–p97 complexes. Disordered regions in p47 are shown to be critical in directing intra-p47 and p47–p97 interactions via a pair of previously unidentified linear motifs. One of these, an SHP domain, regulates p47 binding to p97 in a manner that depends on the nucleotide state of p97. NMR and electron cryomicroscopy data have been used as restraints in molecular dynamics trajectories to develop structural ensembles for p47–p97 complexes in adenosine diphosphate (ADP)- and adenosine triphosphate (ATP)-bound conformations, highlighting differences in interactions in the two states. Our study establishes the importance of intrinsically disordered regions in p47 for the formation of functional p47–p97 complexes.

VCP / p97是蛋白质变形的关键酶，通过与针对特定细胞任务的蛋白质衔接子相互作用来调节。一种这样的衔接子，p47，与p97形成复合物以指导脂质膜重塑。在这里，我们使用NMR和其他生物物理方法来研究p47和p47-p97复合物的结构动力学。p47中的无序区域显示出通过一对先前未识别的线性基序在指导p47和p47-p97内部相互作用中至关重要。其中之一，即SHP域，以依赖于p97核苷酸状态的方式调节p47与p97的结合。核磁共振和电子低温显微术数据已被用作分子动力学轨迹的约束条件，以开发二磷酸腺苷（ADP）和三磷酸腺苷（ATP）结合构象的p47-p97配合物的结构体，突出显示两种状态下的互动差异。我们的研究确立了p47内在无序区域对于功能性p47-p97复合物形成的重要性。