A cysteine-based molecular code informs collagen C-propeptide assembly.
A cysteine-based molecular code informs collagen C-propeptide assembly.
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DOI：
10.1038/s41467-018-06185-2
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发表时间：
2018-10-11
影响因子：
16.6
通讯作者：
Shoulders MD
中科院分区：
文献类型：
--
作者：
DiChiara AS;Li RC;Suen PH;Hosseini AS;Taylor RJ;Weickhardt AF;Malhotra D;McCaslin DR;Shoulders MD
Fundamental questions regarding collagen biosynthesis, especially with respect to the molecular origins of homotrimeric versus heterotrimeric assembly, remain unanswered. Here, we demonstrate that the presence or absence of a single cysteine in type-I collagen’s C-propeptide domain is a key factor governing the ability of a given collagen polypeptide to stably homotrimerize. We also identify a critical role for Ca2+ in non-covalent collagen C-propeptide trimerization, thereby priming the protein for disulfide-mediated covalent immortalization. The resulting cysteine-based code for stable assembly provides a molecular model that can be used to predict, a priori, the identity of not just collagen homotrimers, but also naturally occurring 2:1 and 1:1:1 heterotrimers. Moreover, the code applies across all of the sequence-diverse fibrillar collagens. These results provide new insight into how evolution leverages disulfide networks to fine-tune protein assembly, and will inform the ongoing development of designer proteins that assemble into specific oligomeric forms. Collagen proteins assemble into trimers from distinct monomers with high specificity, yet the molecular basis for this specificity remains unclear. Here the authors demonstrate the crucial role of conserved C-terminal domain cysteine residues and calcium in homotrimeric procollagen assembly.
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影响因子：
4.8
作者：
Han, Sejin;Makareeva, Elena;Leikin, Sergey
通讯作者：
Leikin, Sergey
DOI：
10.1038/nrm3902
发表时间：
2014-12
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Mouw JK;Ou G;Weaver VM
通讯作者：
Weaver VM
影响因子：
15
作者：
Fallas, Jorge A.;Lee, Michael A.;Hartgerink, Jeffrey D.
通讯作者：
Hartgerink, Jeffrey D.
影响因子：
4
作者：
Bygrave, FL;Benedetti, A
通讯作者：
Benedetti, A
影响因子：
56.9
作者：
BELLA, J;EATON, M;BERMAN, HM
通讯作者：
BERMAN, HM