Repeat motions and backbone flexibility in designed proteins with different numbers of identical consensus tetratricopeptide repeats
Repeat motions and backbone flexibility in designed proteins with different numbers of identical consensus tetratricopeptide repeats
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DOI：
10.1021/bi060819a
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发表时间：
2006-10-03
期刊：
影响因子：
2.9
通讯作者：
Stone, Martin J.
中科院分区：
文献类型：
--
作者：
Cheng, Cecilia Y.;Jarymowycz, Virginia A.;Stone, Martin J.
四肽重复序列（tetratricopeptide repeat， TPR）是一个有34个残基的螺旋-螺旋-螺旋基序，在多种蛋白质中以三个或更多串联重复序列的形式出现。我们利用N-15核磁共振弛豫测量确定了含有两个或三个共识TPR重复序列（分别为CTPR2和CPTR3）的蛋白质的重复运动和骨干波动。根据这些数据计算出的每个TPR蛋白中每个重复序列的旋转扩散张量表明，同一蛋白中不同重复序列之间存在高度的运动相关性。这与目前流行的观点一致，即重复蛋白，如CTPR2和CTPR3，表现为单个合作折叠结构域。采用Lipari-Szabo无模型形式确定了主干NH基团的内部运动。对于大多数残基，内部运动和整体旋转翻滚对观测到的磁弛豫的影响之间存在明显的分离。局部内部运动在大多数螺旋元件中受到高度限制，在连杆元件中具有稍大的灵活性。CTPR2和CTPR3的比较表明，在CTPR2的c端（溶剂化螺旋之前）添加一个TPR重复序列会略微降低前面螺旋的柔韧性。
The tetratricopeptide repeat (TPR) is a 34-residue helix-turn-helix motif that occurs as three or more tandem repeats in a wide variety of proteins. We have determined the repeat motions and backbone fluctuations of proteins containing two or three consensus TPR repeats (CTPR2 and CPTR3, respectively) using N-15 NMR relaxation measurements. Rotational diffusion tensors calculated from these data for each repeat within each TPR protein indicate that there is a high degree of motional correlation between different repeats in the same protein. This is consistent with the prevailing view that repeat proteins, such as CTPR2 and CTPR3, behave as single cooperatively folded domains. The internal motions of backbone NH groups were determined using the Lipari-Szabo model-free formalism. For most residues, there was a clear separation between the influence of internal motion and the influence of global rotational tumbling on the observed magnetic relaxation. The local internal motions are highly restricted in most of the helical elements, with slightly greater flexibility in the linker elements. Comparisons between CTPR2 and CTPR3 indicate that an addition of a TPR repeat to the C-terminus (before the solvation helix) of CTPR2 slightly reduces the flexibility of the preceding helix.