Three-dimensional structure topology of the calreticulin P-domain based on NMR assignment
Three-dimensional structure topology of the calreticulin P-domain based on NMR assignment
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DOI：
10.1016/s0014-5793(00)02382-6
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发表时间：
2001-01-12
期刊：
影响因子：
3.5
通讯作者：
Wüthrich, K
中科院分区：
文献类型：
--
作者：
Ellgaard, L;Riek, R;Wüthrich, K
钙网蛋白（CRT）是一种丰富的内质网分子伴侣。它的中央富含脯氨酸的P-结构域，包括残基189 - 288，含有两个重复序列（1型和2型）中的每一个的三个拷贝，它们以特征性的"111222"模式排列。在这里，我们表明，CRT（189 - 288）的三维结构包含一个单一的发夹折叠形成的整个多肽链。发夹底部的环由残基227 - 247组成，并且由残基224 - 226和248 - 250的反平行β折叠闭合。另外两个β折叠包含残基207 - 209和262 - 264以及190 - 192和276 - 278。发夹N末端部分β链的17个残基间距和C末端部分的14个残基间距反映了1型和2型序列重复的长度。作为这种拓扑结构的结果，在发夹的N-末端部分中分离β-链的肽段可能形成凸起以容纳额外的残基。这些结果是基于CRT（189 - 288）的几乎完整的序列特异性NMR分配，其使用C-13/N-15标记的蛋白质的标准NMR技术和核Overhauser增强上限距离约束的集合获得。(C)2001年欧洲生物化学学会联合会。由Elsevier Science B.V.出版，版权所有。
Calreticulin (CRT) is an abundant molecular chaperone of the endoplasmic reticulum. Its central, proline-rich P-domain, comprising residues 189-288, contains three copies of each of two repeat sequences (types 1 and 2), which are arranged in a characteristic '111222' pattern. Here we show that the three-dimensional structure of CRT(189-288) contains a single hairpin fold formed by the entire polypeptide chain. The loop at the bottom of the hairpin consists of residues 227-247, and is closed by an anti-parallel beta -sheet of residues 224-226 and 248-250. Two additional beta -sheets contain residues 207-209 and 262-264, and 190-192 and 276-278, The 17-residue spacing of the beta -strands in the N-terminal part of the hairpin and the 14-residue spacing in the C-terminal part reflect the length of the type 1 and type 2 sequence repeats. As a consequence of this topology the peptide segments separating the beta -strands in the N-terminal part of the hairpin are likely to form bulges to accommodate the extra residues. These results are based on nearly complete sequence-specific NMR assignments for CRT(189-288), which were obtained using standard NMR techniques with the C-13/N-15-labeled protein, and collection of nuclear Overhauser enhancement upper distance constraints. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.