Dynamic influences on a high-affinity, high-specificity interaction involving the C-terminal SH3 domain of P67phox
Dynamic influences on a high-affinity, high-specificity interaction involving the C-terminal SH3 domain of P67phox
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DOI：
10.1021/bi030268d
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发表时间：
2004-06-29
期刊：
影响因子：
2.9
通讯作者：
Ghose, R
中科院分区：
文献类型：
--
作者：
Dutta, K;Shi, HH;Ghose, R
p67（phox）的C-末端Src同源性3（SH 3）结构域p67（phox）SH 3（C）与来自p47（phox）的C-末端区域的32个残基的高亲和力（Kd = 24 nM）肽Pf复合的骨架动力学分析被呈现。本文代表了第一次详细分析的骨干动力学和配体诱导的变化，其中的高亲和力，高特异性的相互作用，涉及SH 3结构域。的动态功能进行了比较，在高亲和力，高特异性的C-末端Src激酶（Csk-SH 3）和脯氨酸富集的磷酸酶（PEP）的脯氨酸丰富的肽之间的相互作用的SH 3结构域。这两个系统共享共同的动态特征，特别是在典型的PxxP基序识别表面，其中缓慢的微毫秒时间尺度的动态持续复合物的形成，特别是在涉及配体识别和稳定的SH 3折叠的几个残基。这些残基在SH 3结构域中高度保守。Ile 505位于p67（phox）SH 3（C）上的PxxP识别基序之外，是赋予p67（phox）SH 3（C）/Pf相互作用高特异性的关键，在复合物形成时变得更加无序。这种行为类似于在Csk-SH 3中构成特异性表面的残基中所见的行为。
An analysis of the backbone dynamics of the C-terminal Src homology 3 (SH3) domain of p67(phox), p67(phox)SH3(C), in complex with a 32-residue high-affinity (K-d = 24 nM) peptide, Pf, from the C-terminal region of p47(phox) is presented. This paper represents the first detailed analysis of the backbone dynamics and the ligand-induced changes therein of a high-affinity, high-specificity interaction involving an SH3 domain. The dynamic features are compared with those in the high-affinity, highly specific interaction between the SH3 domain of C-terminal Src kinase (Csk-SH3) and a proline-rich peptide from proline-enriched phosphatase (PEP). Both systems share common dynamic features especially in the canonical PxxP motif recognition surface where slow micro- to millisecond time scale dynamics persist on complex formation especially in several residues that are implicated in ligand recognition and in stabilizing the SH3 fold. These residues are highly conserved in SH3 domains. Ile505, which lies outside the PxxP recognition motif on p67phoxSH3(C) and is key in conferring high specificity to the p67(phox)SH3(C)/Pf interaction, becomes more disordered upon complex formation. This behavior is similar to that seen in the residues that constitute the specificity surface in Csk-SH3.