Asakura Tetsuo, Ohgo Kosuke, Ishida Teppei, Taddei Paola, Monti Patrizia, Kishore Raghuvansh
Department of Biotechnology, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan.
Biomacromolecules. 2005 Jan-Feb;6(1):468-74. doi: 10.1021/bm049487k.
Bombyx mori silk fibroin molecule is known to exist in two distinct structural forms: silk I (unprocessed silk fibroin) and silk II (processed silk fibroin). Using synthetic peptides, we attempt to explore the structural role played by Ser and Tyr residues on the appearance of silk I structural form of the fibroin. Twelve selected peptides (1-12) incorporating Ser and Tyr residues in the (Ala-Gly)(n) copolypeptide, that is, the sequences mimicking the primary structure of B. mori silk fibroin molecule, have been investigated under the silk I state, employing high-resolution (13)C cross-polarization/magic-angle spinning (CP/MAS) NMR spectroscopy. To acquire the silk I structural form, all the peptides were dissolved in 9 M LiBr and then dialyzed extensively against water, as established previously for the synthetic (Ala-Gly)(15) copolypeptide and B. mori silk fibroin. The diagnostic line shape of the Ala C(beta) peaks and the conformation-dependent (13)C chemical shifts of Ala and Gly resonances are presented to analyze and characterize the structural features. The results indicate that the incorporation of one Ser and/or one Tyr residue(s) at selected position in the basic (Ala-Gly)(15) sequence tend to retain predominantly the silk I structure. Conversely, the repeat pentameric and octameric Ala-Gly-Ser-Gly-Ala-Gly sequences, for example, (Ala-Gly-Ser-Gly-Ala-Gly)(5) or (Ala-Gly-Ser-Gly-Ala-Gly)(8), preferred predominantly the silk II form. The peptide sequences incorporating Ser and Tyr residue(s) into repeat Ala-Gly-Ser-Gly-Ala-Gly sequences, however, adopted the silk II structure with certain content structural heterogeneity or randomness, more pronounced for specific peptides studied. Interestingly, the crystalline Cp fraction of B. mori silk fibroin, when mixed with (Ala-Gly-Ser-Gly-Ala-Gly)(5) sequence in a 5:1 molar ratio, dissolved in 9 M LiBr, and dialyzed against distilled water, favor the silk I form. The finding tends to suggest that the less stable silk I form in (Ala-Gly-Ser-Gly-Ala-Gly)(n) sequences is likely to be induced and facilitated via intermolecular interactions with the Cp fraction, which predominantly prefers the silk I form under similar conditions; however, the hydrogen-bond formation involving O(gamma)H groups of the Ser residues may have some implications.
丝I(未加工的丝素蛋白)和丝II(加工后的丝素蛋白)。我们使用合成肽,试图探索丝氨酸(Ser)和酪氨酸(Tyr)残基在丝素蛋白丝I结构形式出现过程中所起的结构作用。在丝I状态下,我们利用高分辨率的碳-13交叉极化/魔角旋转(CP/MAS)核磁共振光谱,研究了12种选定的肽(1 - 12),这些肽在(丙氨酸-甘氨酸)(n)共多肽中包含Ser和Tyr残基,即模拟家蚕丝素蛋白分子一级结构的序列。为了获得丝I结构形式,所有肽都溶解在9M的溴化锂中,然后按照之前合成的(丙氨酸-甘氨酸)(15)共多肽和家蚕丝素蛋白的方法,用大量水进行透析。通过展示丙氨酸Cβ峰的诊断线形以及丙氨酸和甘氨酸共振的构象依赖性碳-13化学位移,来分析和表征结构特征。结果表明,在基本的(丙氨酸-甘氨酸)(15)序列中的选定位置引入一个Ser和/或一个Tyr残基倾向于主要保留丝I结构。相反,例如重复的五聚体和八聚体丙氨酸-甘氨酸-丝氨酸-甘氨酸-丙氨酸-甘氨酸序列,即(丙氨酸-甘氨酸-丝氨酸-甘氨酸-丙氨酸-甘氨酸)(5)或(丙氨酸-甘氨酸-丝氨酸-甘氨酸-丙氨酸-甘氨酸)(8),则主要倾向于丝II形式。然而,将Ser和Tyr残基引入重复的丙氨酸-甘氨酸-丝氨酸-甘氨酸-丙氨酸-甘氨酸序列的肽序列,采用了具有一定结构异质性或随机性的丝II结构,对于所研究的特定肽更为明显。有趣的是,当家蚕丝素蛋白的结晶性Cp部分与(丙氨酸-甘氨酸-丝氨酸-甘氨酸-丙氨酸-甘氨酸)(5)序列以5:1的摩尔比混合,溶解在9M的溴化锂中,并对蒸馏水进行透析时,有利于丝I形式。这一发现倾向于表明,在(丙氨酸-甘氨酸-丝氨酸-甘氨酸-丙氨酸-甘氨酸)(n)序列中较不稳定的丝I形式可能通过与Cp部分的分子间相互作用被诱导和促进,在类似条件下Cp部分主要倾向于丝I形式;然而,涉及Ser残基OγH基团的氢键形成可能有一定影响。