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SOLUTION STRUCTURE OF RECOMBINANT HUMAN INTERLEUKIN-6

机译:重组人白介素-6的溶液结构

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Interleukin-6 (IL-6) is a 185 amino-acid cytokine which exerts multiple biological effects in vivo and whose dysregulation underlies several disease processes The solution structure of recombinant human interleukin-6 has now been determined using heteronuclear three and four-dimensional NMR spectroscopy. The structure of the molecule was determined using 3044 distance and torsion restraints derived by NMR spectroscopy to generate an ensemble of 32 structures using a combined distance geometry/simulated annealing protocol. The protein contains five alpha-helices interspersed with variable-length loops; four of these helices constitute a classical four-helix bundle with the fifth helix located in the CD loop. There were no distance violations greater than 0.3 Angstrom in any of the final 32 structures and the ensemble has an average-to-the-mean backbone root-mean-square deviation of 0.50 Angstrom for the core four-helix bundle. Although the amino-terminal 19 amino acids are disordered in solution, the remainder of the molecule has a well defined structure that shares many features displayed by other long-chain four-helix bundle cytokines. The high-resolution NMR structure of hIL-6 is used to rationalize available mutagenesis data in terms of a heteromeric receptor complex. (C) 1997 Academic Press Limited. [References: 81]
机译:白细胞介素6(IL-6)是一种185个氨基酸的细胞因子,可在体内发挥多种生物学作用,其失调是多种疾病过程的基础。现已使用异核3维和4维NMR确定了重组人白细胞介素6的溶液结构。光谱学。使用3044距离和扭转约束条件确定分子的结构,该距离和扭转约束条件是通过NMR光谱学/模拟退火方案结合使用NMR光谱法生成32个结构的整体。该蛋白含有五个α-螺旋,它们之间穿插有可变长度的环。这些螺旋中的四个螺旋构成一个经典的四螺旋束,第五个螺旋位于CD环中。最终的32个结构中任何一个都没有大于0.3埃的距离冲突,并且该集合对于核心四螺旋束的平均主干均方根方差为0.50埃。尽管溶液中氨基末端的19个氨基酸无序,但分子的其余部分具有定义明确的结构,该结构具有其他长链四螺旋束细胞因子所展现的许多特征。 hIL-6的高分辨率NMR结构用于根据异聚受体复合物合理化可用的诱变数据。 (C)1997 Academic Press Limited。 [参考:81]

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