一级结构Protein primary structure

序列书写以三字母或单字母代码从 N 端开始，如 MVLSPADKT…。1961 年安芬森发现变性的核糖核酸酶在去除变性剂后能自发重新折叠并恢复活性，证明“序列决定结构”（安芬森原理），他获 1972 年诺贝尔化学奖。一个氨基酸的改变就可能引起疾病，如镰状细胞贫血中血红蛋白 β 链第 6 位谷氨酸变为缬氨酸。同源蛋白质序列的比较可用来推断进化关系。

Sequences are written from the N-terminus in three- or one-letter codes, such as MVLSPADKT…. In 1961 Anfinsen found that denatured ribonuclease refolds spontaneously and regains activity when the denaturant is removed, showing that sequence determines structure (Anfinsen's principle); he shared the 1972 Nobel Prize in Chemistry. A single change can cause disease, as when glutamate 6 of the haemoglobin β chain becomes valine in sickle-cell anaemia. Comparing homologous sequences reveals evolutionary relationships.

1945–1955 年桑格用 2,4-二硝基氟苯标记 N 端、部分水解和纸色谱拼接片段，测定了牛胰岛素两条链（A 链 21、B 链 30 个残基）的全序列，证明蛋白质有确定的序列，获 1958 年诺贝尔化学奖。1950 年埃德曼发明逐个切下 N 端氨基酸的埃德曼降解法，并发展为自动测序仪。如今主要通过基因测序推导，或用串联质谱测定。

From 1945 to 1955 Sanger labelled N-termini with 2,4-dinitrofluorobenzene, partially hydrolysed the chains and pieced fragments together by paper chromatography to determine the complete sequence of bovine insulin (A chain 21 and B chain 30 residues), proving proteins have defined sequences; he received the 1958 Nobel Prize in Chemistry. Edman's 1950 method removes N-terminal residues one at a time and was later automated. Today sequences are mostly deduced from DNA or determined by tandem mass spectrometry.

一级结构还包括磷酸化、糖基化、乙酰化、二硫键和蛋白酶切割等翻译后修饰。例如胰岛素原经切除 C 肽后形成由两个二硫键连接的 A、B 两链。这些修饰大大扩展了蛋白质的功能多样性。

Primary structure also includes post-translational modifications such as phosphorylation, glycosylation, acetylation, disulfide bonds and proteolytic cleavage. Proinsulin, for example, loses its C-peptide to leave A and B chains joined by two disulfide bonds. Such modifications greatly expand protein functional diversity.