High-resolution solution structure of the 18 kDa substrate-binding domain of the mammalian chaperone protein Hsc70
High-resolution solution structure of the 18 kDa substrate-binding domain of the mammalian chaperone protein Hsc70
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DOI：
10.1006/jmbi.1999.2776
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发表时间：
1999-06-25
影响因子：
5.6
通讯作者：
Zuiderweg, ERP
中科院分区：
文献类型：
--
作者：
Morshauser, RC;Hu, WD;Zuiderweg, ERP
哺乳动物伴侣蛋白Hsc 70的70 kDa的热休克类（HSP 70）的底物结合域的三维结构。该结构域包括残基383-540（18 kDa），并且是伴侣蛋白与底物蛋白和肽结合所必需的。高分辨率NMR溶液结构基于4150个实验距离约束，导致骨架原子的平均均方根精度为0.38埃，β-夹心子域中所有原子的平均均方根精度为0.76埃。观察到该蛋白通过分子相互作用结合其疏水底物结合沟中的残基Leu 539。螺旋闩锁的位置显着不同，从所观察到的同源原核分子伴侣DnaK的晶体和溶液结构。在Hsc 70结构中，螺旋位于疏水沟中，并通过埋藏的盐桥锚定。参与这种盐桥的残基似乎对蛋白质的变构功能很重要。提出了一种结构域间变构调节底物结合的机制。它涉及螺旋结构域的大规模运动，重新定义了使这种运动成为可能的铰链区的位置。(C)北京：科学出版社.
The three-dimensional structure for the substrate-binding domain of the mammalian chaperone protein Hsc70 of the 70 kDa heat shock class (HSP70) is presented. This domain includes residues 383-540 (18 kDa) and is necessary for the binding of the chaperone with substrate proteins and peptides. The high-resolution NMR solution structure is based on 4150 experimental distance constraints leading to an average root-mean-square precision of 0.38 Angstrom for the backbone atoms and 0.76 Angstrom for all atoms in the beta-sandwich sub-domain. The protein is observed to bind residue Leu539 in its hydrophobic substrate-binding groove by inh a molecular interaction. The position of a helical latch differs dramatically from what is observed in the crystal and solution structures of the homologous prokaryotic chaperone DnaK. Ln the Hsc70 structure, the helix lies in a hydrophobic groove and is anchored by a buried salt-bridge. Residues involved in this salt-bridge appear to be important for the allosteric functioning of the protein. A mechanism for interdomain allosteric modulation of substrate-binding is proposed. It involves large-scale movements of the helical domain, redefining the location of the hinge area that enables such motions. (C) 1999 Academic Press.