蛋白质的结构 Structure of Proteins 第3章 蛋白质 Chapter 3 Protein 蛋白质的结构 Structure of Proteins Zhong Kai Teaching Group of Physiology and Biochemistry

Primary Structure of Proteins 蛋白质的一级结构 Primary Structure of Proteins

多肽链上氨基酸的种类及排列顺序，包括二硫键的位置。 Primary structure is the sequence of amino acid residues linked by peptide bond and the location of disulfide bonds in a protein molecule.

Primary structure of insulin 胰岛素的一级结构 Primary structure of insulin

蛋白质的一级结构书写惯例是：从左向右，按照由N端向C端的方向书写。 A convention has to be followed in writing the primary structure, upon which sequence is read from the amino end to the carboxyl end(羧基端), corresponding to direction from left to right.

Stabilized by covalent bonds(共价键), especially by peptide bonds(肽键). 一级结构由共价键，特别是肽键来稳定 Stabilized by covalent bonds(共价键), especially by peptide bonds(肽键).

肽键 Peptide Bond

是多肽链中将两个相邻的氨基酸残基连在一起的共价键。 A covalent bond linking the two neighboring residues in peptides.

肽平面 Peptide plane

蛋白质中肽键的C、N及其相连的4个原子组成肽单元 。这几个原子形成一个平面，称为肽平面。 C-N bond was rigid and coplanar with the 4 atoms associated with it. This plane is termed peptide unit or peptide plane.

Single bond 0.147nm Double bond 0.128nm

肽键的键长短于典型的单键，长于典型的双键 Shorter than a typical single bond but longer than a typical double bond.

Has partial double bond character 具有部分双键的性质 Has partial double bond character

What’s the difference between the single bond and the double bond? 问题：单键与双键最重要的区别是什么？ What’s the difference between the single bond and the double bond?

双键的性质使肽键不能旋转，并导致与肽键相关的6个原子共平面。 Due to the double bond character, it can’t rotate and the six atoms of the peptide bond group are always in the same plane(coplanar).

两面角 dihedral angle

肽键不能旋转，但与α-碳相连的2个键是单键，因此可以自由旋转。 Rotation can only occur around the two bonds connected to the C α atom.

Cα-N之间称φ角，在Cα-C之间称ψ角，这就是α-碳原子上的一对二面角。这对二面角决定了相邻肽平面的相对位置。 Rotation around Cα-N is called φ, and rotation around Cα-C is called ψ. These two bond angles altogether are called dihedral angle(二面角).

由于侧链之间的空间位阻，某些φ， ψ是不允许的。 Some(φ, ψ) are forbidden owing to steric hindrance(位阻) between R groups.

Secondary Structure of Proteins 蛋白质的二级结构 Secondary Structure of Proteins

蛋白质的二级结构是指多肽链的主链在局部形成的有规律的盘绕或折叠，其稳定性由主链上的氢键决定。 Regular repeating folding structure of the polypeptide chain as a result of hydrogen bonding in the backbone.

主链 Backbone

有规律 Regular α-螺旋 Alpha helix β-折叠 Beta sheet β-转角 Beta turn

无规卷曲 Random coils

α-螺旋 Alpha Helix

最先由Pauling提出，他因此得到他的第一次诺贝尔奖。 Proposed by Linus Pauling, who won his first Nobel Prize for this.

American chemist Linus Pauling

为螺旋结构，螺旋的方向是右手的。 The alpha helix is a helical structure. All alpha helixes in proteins are right-handed.

由主链上的氢键稳定，氢键的构成是由n位肽键上的羰基O与n+3位肽键上的NH形成氢键。 Stabilized by backbone H bonds. H-bond patterns of the alpha helix: carbonyl(羰基) oxygen of the nth residue forms H-bond with amide proton of the (n+3)th residue.

C 端 图例： 黑色—碳原子 红色—羰基氧 黄色—R侧链 蓝色—酰胺N 白色—氢原子 N 端

α-螺旋相关参数：每圈3.6个氨基酸残基，螺距为0.54nm, 相邻两个氨基酸之间的距离是0.15nm. Some parameters about alpha helix: Residues per turn: 3.6 Rise per residue: 0.15nm Rise per turn(pitch): 3.6×0.15=0.54nm .

R groups are displayed on the surface of the helix.

双亲性α-螺旋：既含有亲水侧链，又含有疏水侧链，而且其分布有规律，亲水基团集中在一面，疏水基团集中在另一面。 Contains both hydrophilic(亲水的) amino acids and hydrophobic(疏水的) amino acids, which are distributed on the different sides regularly. .

不同的氨基酸形成α-螺旋的倾向性有别：Glu，Met，Ala和Leu等有利于形成α-螺旋，而Pro和Gly则不利。 Glu, Met, Ala, Leu have high propensities in alpha helix; Pro and Gly usually don’t favor formation of alpha helix. .

β-pleated Sheet or β Sheet β-折叠 β-pleated Sheet or β Sheet

β股之间通过主链之间的氢键相连，成锯齿状展开 β strands are connected by backbone hydrogen bonds, forming a generally twisted pleated sheet.

Composed of at least two β strands β-折叠至少由2个β股组成 Composed of at least two β strands β 股的来源 The origin of β strands

β strands may be parallel or anti parallel β股之间可以是平行的，或反平行的 β strands may be parallel or anti parallel

β-折叠结构中氨基酸残基之间的距离：反平行的是0.347nm，平行的是0.325nm。 Rise per residue: 0.347nm for antiparallel strands; 0.325 nm for parallel strands.

R基团在主链上上下交替排列，约与折叠的平面垂直 The side chains point outwards from the pleats, roughly perpendicularly(垂直地)to the plane of the sheet, successive residues points outwards on alternating faces of the sheet.

β-转角 Beta-Turn

β-转角由4个氨基酸残基组成，第1个氨基酸残基的羰基氧和第4个氨基酸残基的亚氨基的氢原子形成氢键。 Beta-Turn is composed of four successive amino acid residues. The carbonyl oxygen of the nth residue forms H-bond with the amide proton of the (n+3)th residue.

形状像英文字母U，因此可导致肽链主链发生180度方向的改变。 It looks like English letter U and can cause 180 degree change of direction of the backbone.

富含脯氨酸和甘氨酸的4个氨基酸更容易形成β-转角结构 Proline and glycine have high propensity for beta-turn.

无规卷曲 Random Coil

模体 Motif

Formerly known as super-secondary structure. 以前称为超二级结构 Formerly known as super-secondary structure.

一些具有特定几何排列的二级结构的简单组合。 Motif is a simple combination of a few secondary structural elements with a specific geometric arrangement.

螺旋-环-螺旋（helix-turn-helix） 常见的模体有： 折叠-螺旋-折叠（βαβ） 螺旋-环-螺旋（helix-turn-helix） 发卡结构（hairpin） 希腊钥匙（Greek key）

结构域 Domain

结构域是指蛋白质分子上相对独立、稳定的球状结构单位。 Domain refers to the distinct, stable globular units or folds within a single polypeptide.

丙酮酸激酶的一个结构域 免疫球蛋白的一个结构域

大片段 / Klenow 片段 小片段 N 端 C 端 木瓜蛋白酶 604个氨基酸 323个氨基酸 DNA聚合酶活性   5 核酸外切酶活性 5  核酸外切酶活性

Tertiary Structure of Protein 蛋白质的三级结构 Tertiary Structure of Protein

三级结构是指蛋白质所有原子在三维空间上的排布。 The three dimensional arrangement of all atoms in a given protein is referred to tertiary structure.

肌红蛋白的三级结构 Tertiary structure of myoglobin

稳定三级结构的化学键包括：氢键、疏水键、范德华力、离子键和二硫键，其中疏水作用力是最重要的化学键。 Chemical bonds stabilizing tertiary structure include hydrogen bond, hydrophobic interaction, Van der Waals interaction, ionic bond and disulfide bond.

Quaternary Structure of Protein 蛋白质的四级结构 Quaternary Structure of Protein

并不是所有蛋白质都具有四级结构。通常满足2个条件，才认为蛋白质具有四级结构：1、至少含有2条多肽链。2、肽链之间不允许有共价键，即二硫键。 Not all proteins have quaternary structure. Proteins possessing quaternary structure have to satisfy two conditions: 1. contain at least 2 polypeptide chain; 2. no covalent bonds-disulfide bonds between polypeptide chains.

肌红蛋白、血红蛋白、抗体、胰岛素这四种蛋白质中哪一种具有四级结构？ Which one has quaternary structure among myoglobin, hemoglobin, antibody, and insulin?

构成四级结构的每条多肽链称为一个亚基。亚基可以相同，也可能不同。例如，血红蛋白由2个α亚基，2个β亚基组成。 Each polypeptide chain consisting quaternary structure is known as subunit. For example, homoglobin is composed of two alpha chains and 2 beta chains.

Quaternary structure of hemoglobin 血红蛋白的四级结构 Quaternary structure of hemoglobin

构成四级结构的亚基数目以及它们之间的排布和相互作用。 The number, arrangement, and interaction of these subunits are referred to quaternary structure of protein.