Department of Biochemistry & Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia.
SAXS/WAXS, Australian Synchrotron, Clayton, Australia.
FEBS Lett. 2019 Mar;593(5):533-542. doi: 10.1002/1873-3468.13329. Epub 2019 Feb 2.
Scribble (SCRIB) is an important adaptor protein that controls the establishment and maintenance of apico-basal cell polarity. To better understand how SCRIB controls cell polarity signalling via its PDZ domains, we investigated human SCRIB interactions with adenomatous polyposis coli (APC). We show that SCRIB PDZ1, PDZ2 and PDZ3 are the major interactors with the APC PDZ-binding motif (PBM), whereas SCRIB PDZ4 does not show detectable binding to APC. We then determined the crystal structure of SCRIB PDZ1 domain bound to the APC PBM. Our findings reveal a previously unreported pattern of interactions between the SCRIB PDZ domain region with the C-terminal PDZ binding motif of APC, where SCRIB PDZ1 domain is the highest affinity site.
Scribble (SCRIB) 是一种重要的衔接蛋白，它控制着顶端-基底细胞极性的建立和维持。为了更好地理解 SCRIB 如何通过其 PDZ 结构域控制细胞极性信号，我们研究了人 SCRIB 与腺瘤性结肠息肉病基因 (APC) 的相互作用。我们发现 SCRIB PDZ1、PDZ2 和 PDZ3 是与 APC PDZ 结合基序 (PBM) 主要相互作用的结构域，而 SCRIB PDZ4 与 APC 没有可检测到的结合。然后，我们测定了 SCRIB PDZ1 结构域与 APC PBM 结合的晶体结构。我们的研究结果揭示了 SCRIB PDZ 结构域区域与 APC C 末端 PDZ 结合基序之间以前未报道的相互作用模式，其中 SCRIB PDZ1 结构域是亲和力最高的位点。
