Nolte R T, Eck M J, Schlessinger J, Shoelson S E, Harrison S C
Howard Hughes Medical Institute and Laboratory of Molecular Medicine, Children's Hospital, Boston, Massachusetts 02115, USA.
Nat Struct Biol. 1996 Apr;3(4):364-74. doi: 10.1038/nsb0496-364.
Crystal structures of the amino-terminal SH2 domain of the p85alpha subunit of phosphatidylinositol (PI) 3-kinase, alone and in complex with phosphopeptides bearing pTyr-Met/Val-Xaa-Met motifs, show that phosphopeptides bind in the two-pronged manner seen in high-affinity Lck and Src SH2 complexes, with conserved interactions between the domain and the peptide segment from phosphotyrosine to Met+3. Peptide binding requires the rearrangement of a tyrosyl side chain in the BG loop to create the hydrophobic Met+3 binding pocket. The structures suggest a mechanism for the biological specificity exhibited by PI 3-kinase in its interactions with phosphoprotein partners.
磷脂酰肌醇（PI）3激酶p85α亚基氨基末端SH2结构域单独以及与带有pTyr-Met/Val-Xaa-Met基序的磷酸肽形成复合物时的晶体结构表明，磷酸肽以在高亲和力Lck和Src SH2复合物中所见的双叉方式结合，该结构域与从磷酸酪氨酸到Met+3的肽段之间存在保守相互作用。肽结合需要BG环中的酪氨酸侧链重排以形成疏水的Met+3结合口袋。这些结构提示了PI 3激酶在与磷蛋白伴侣相互作用中所表现出的生物学特异性的一种机制。
