Ghose R, Shekhtman A, Goger M J, Ji H, Cowburn D
The Rockefeller University, 1230 York Avenue, New York, New York 10021-6399, USA.
Nat Struct Biol. 2001 Nov;8(11):998-1004. doi: 10.1038/nsb1101-998.
C-terminal Src kinase (Csk) takes part in a highly specific, high affinity interaction via its Src homology 3 (SH3) domain with the proline-enriched tyrosine phosphatase PEP in hematopoietic cells. The solution structure of the Csk-SH3 domain in complex with a 25-residue peptide from the Pro/Glu/Ser/Thr-rich (PEST) domain of PEP reveals the basis for this specific peptide recognition motif involving an SH3 domain. Three residues, Ala 40, Thr 42 and Lys 43, in the SH3 domain of Csk specifically recognize two hydrophobic residues, Ile 625 and Val 626, in the proline-rich sequence of the PEST domain of PEP. These two residues are C-terminal to the conventional proline-rich SH3 domain recognition sequence of PEP. This interaction is required in addition to the classic polyproline helix (PPII) recognition by the Csk-SH3 domain for the association between Csk and PEP in vivo. NMR relaxation analysis suggests that Csk-SH3 has different dynamic properties in the various subsites important for peptide recognition.
C 端 Src 激酶(Csk)通过其Src 同源 3(SH3)结构域与造血细胞中富含脯氨酸的酪氨酸磷酸酶 PEP 进行高度特异性、高亲和力的相互作用。Csk-SH3 结构域与来自 PEP 的富含脯氨酸/谷氨酸/丝氨酸/苏氨酸(PEST)结构域的 25 个残基肽形成的复合物的溶液结构揭示了这种涉及 SH3 结构域的特异性肽识别基序的基础。Csk 的 SH3 结构域中的三个残基,即 Ala 40、Thr 42 和 Lys 43,特异性识别 PEP 的 PEST 结构域富含脯氨酸序列中的两个疏水残基,Ile 625 和 Val 626。这两个残基位于 PEP 传统富含脯氨酸的 SH3 结构域识别序列的 C 端。除了 Csk-SH3 结构域对经典多聚脯氨酸螺旋(PPII)的识别外,这种相互作用对于体内 Csk 和 PEP 之间的结合也是必需的。核磁共振弛豫分析表明,Csk-SH3 在对肽识别重要的各个亚位点具有不同的动力学性质。