Flinta C, Persson B, Jörnvall H, von Heijne G
Eur J Biochem. 1986 Jan 2;154(1):193-6. doi: 10.1111/j.1432-1033.1986.tb09378.x.
N-terminal methionine removal has been analyzed statistically in a large sample of prokaryotic and eukaryotic cytosolic proteins in an attempt to uncover common sequence determinants. We find that the residue next to the initiator Met is the most important determinant of N-terminal processing: Lys, Arg, Leu and (in prokaryotes) Phe and Ile protect the initiator Met from being removed when next to it in the sequence; Ala, Gly, Pro, Ser, Thr and (in eukaryotes) Val in this position cause its removal. Subsequent acetylation is confirmed to be strongly biased towards Ala, Met and Ser residues; when Met is acetylated, Asp is the predominant penultimate residue in eukaryotes. Also, we find major differences in the relative abundance of the various residues next to the initiator Met between prokaryotes and eukaryotes: prokaryotic proteins are much more biased towards Lys as the Met-protecting residue, and towards Ala when met is to be removed, than eukaryotic ones. Finally, we show that our results can explain a part of the mRNA 'consensus sequence' found around eukaryotic initiator AUG codons.
为了揭示共同的序列决定因素，我们对大量原核和真核细胞溶质蛋白样本中的N端甲硫氨酸去除情况进行了统计分析。我们发现，起始甲硫氨酸旁边的残基是N端加工的最重要决定因素：赖氨酸、精氨酸、亮氨酸以及（在原核生物中）苯丙氨酸和异亮氨酸在序列中紧邻起始甲硫氨酸时可保护其不被去除；此位置的丙氨酸、甘氨酸、脯氨酸、丝氨酸、苏氨酸以及（在真核生物中）缬氨酸会导致其被去除。后续的乙酰化被证实强烈偏向于丙氨酸、甲硫氨酸和丝氨酸残基；当甲硫氨酸被乙酰化时，天冬氨酸是真核生物中主要的倒数第二个残基。此外，我们发现原核生物和真核生物中起始甲硫氨酸旁边各种残基的相对丰度存在重大差异：与真核生物相比，原核生物蛋白质在作为甲硫氨酸保护残基时更偏向于赖氨酸，而在甲硫氨酸要被去除时更偏向于丙氨酸。最后，我们表明我们的结果可以解释在真核生物起始AUG密码子周围发现的部分mRNA“共有序列”。
