Aromatic interactions promote self-association of collagen triple-helical peptides to higher-order structures.
Aromatic interactions promote self-association of collagen triple-helical peptides to higher-order structures.
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DOI：
10.1021/bi900496m
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发表时间：
2009-08-25
期刊：
影响因子：
2.9
通讯作者：
Brodsky, Barbara
中科院分区：
文献类型：
--
作者：
Kar, Karunakar;Ibrar, Sajjad;Nanda, Vikas;Getz, Todd M.;Kunapuli, Satya P.;Brodsky, Barbara
芳香族残基在胶原蛋白的三螺旋结构中相对较少，但它们似乎在更高级的结构和功能中发挥着特殊的作用。从自结合动力学、聚集物种的性质以及这些物种激活血小板聚集的能力等方面研究了芳香族氨基酸在三螺旋多肽自组装中的作用。观察到IV型胶原模型多肽两端的芳香族残基的存在极大地加速了自结合动力学，缩短了滞后时间，并导致了不溶的、明确的线状纤维以及小的可溶聚集体。无论是宏观的可见聚集体还是溶液中的小分子复合体，都能通过血小板上的糖蛋白VI受体诱导血小板聚集。脯氨酸-芳香族CH-⋯π相互作用经常在球状蛋白质和蛋白质复合体中观察到，对整合素结合胶原肽晶体结构的分子堆积研究表明，Phe与邻近的三螺旋分子中的Pro/Hyp相互作用。分离的苯丙氨酸对(Pro-Hyp-Gly)10自结合的抑制作用也支持芳香族氨基酸与三螺旋内亚氨基酸之间的分子间相互作用。考虑到胶原分子表面高比例的Pro和Hyp残基，很可能是亚氨基酸-芳香族CH⋯π相互作用对高阶结构的形成起重要作用。提示非螺旋端肽对I型胶原纤维形成的催化作用是由于端肽中芳香族残基与三螺旋结构中的Pro/Hyp残基之间存在特异的分子间CH⋯π相互作用所致。
Aromatic residues are relatively rare within the collagen triple-helix, but they appear to play a specialized role in higher order structure and function. The role of aromatic amino acids in the self-assembly of triple-helical peptides was investigated in terms of the kinetics of self-association, the nature of aggregated species formed, and the ability of these species to activate platelet aggregation. The presence of aromatic residues on both ends of a type IV collagen model peptide is observed to greatly accelerate the kinetics of self-association, decreasing the lag time and leading to insoluble, well defined linear fibrils as well as small soluble aggregates. Both macroscopic visible aggregates and small multi-molecular complexes in solution are capable of inducing platelet aggregation through the glycoprotein VI receptor on platelets. Proline-aromatic CH⋯π interactions are often observed within globular proteins and in protein complexes, and examination of molecular packing in the crystal structure of the integrin binding collagen peptide shows Phe interacts with Pro/Hyp in a neighboring triple-helical molecule. An intermolecular interaction between aromatic amino acids and imino acids within the triple-helix is also supported by the observed inhibitory effect of isolated Phe amino acids on the self-association of (Pro-Hyp-Gly)10. Given the high fraction of Pro and Hyp residues on the surface of collagen molecules, it is likely that imino acid-aromatic CH⋯π interactions are important in formation of higher order structure. It is suggested that the catalysis of type I collagen fibrillogenesis by non-helical telopeptides is due to specific intermolecular CH⋯π interactions between aromatic residues in the telopeptides and Pro/Hyp residues within the triple-helix.
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影响因子：
20.3
作者：
Jarvis GE;Raynal N;Langford JP;Onley DJ;Andrews A;Smethurst PA;Farndale RW
通讯作者：
Farndale RW
影响因子：
56.9
作者：
BELLA, J;EATON, M;BERMAN, HM
通讯作者：
BERMAN, HM
影响因子：
4.1
作者：
MORTON, LF;HARGREAVES, PG;BARNES, MJ
通讯作者：
BARNES, MJ
影响因子：
4
作者：
FRASER, RDB;TRUS, BL
通讯作者：
TRUS, BL
影响因子：
8
作者：
Kar, Karunakar;Wang, Yuh-Hwa;Brodsky, Barbara
通讯作者：
Brodsky, Barbara