Li S C, Zwahlen C, Vincent S J, McGlade C J, Kay L E, Pawson T, Forman-Kay J D
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Department of Molecular and Medical Genetics, University of Toronto, Ontario, Canada.
Nat Struct Biol. 1998 Dec;5(12):1075-83. doi: 10.1038/4185.
The phosphotyrosine-binding (PTB) domain of Numb, a protein involved in asymmetric cell division, has recently been shown to bind to the adapter protein Lnx through an LDNPAY sequence, to the Numb-associated kinase (Nak) through a sequence that does not contain an NPXY motif and to GP(p)Y-containing peptides obtained from library screening. We show here that these diverse peptide sequences bind with comparable affinities to the Numb PTB domain at a common binding site on the surface of the protein. The NMR structure of the Numb PTB domain in complex with a GPpY-containing peptide reveals a novel mechanism of binding with the peptide in a helical turn that does not hydrogen bond to the PTB domain beta-sheet. These results suggest that PTB domains can potentially have multiple modes of peptide recognition and provide a structural basis from which the multiple functions of the Numb PTB domain during asymmetric cell division could arise.
Numb是一种参与不对称细胞分裂的蛋白质，其磷酸酪氨酸结合（PTB）结构域最近被证明可通过LDNPAY序列与衔接蛋白Lnx结合，通过一个不含NPXY基序的序列与Numb相关激酶（Nak）结合，并与通过文库筛选获得的含GP(p)Y的肽段结合。我们在此表明，这些不同的肽序列以相当的亲和力在该蛋白质表面的一个共同结合位点与Numb PTB结构域结合。Numb PTB结构域与含GPpY的肽段形成的复合物的核磁共振结构揭示了一种在螺旋转角处与该肽段结合的新机制，该螺旋转角不与PTB结构域的β折叠形成氢键。这些结果表明，PTB结构域可能具有多种肽识别模式，并为Numb PTB结构域在不对称细胞分裂过程中的多种功能提供了一个结构基础。
