Transcript 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
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.
胰岛素的一级结构
Primary structure of insulin
S
S
A
Gly Ile Val Glu Gln Cys Cys Ala Ser Val Cys Ser Leu Tyr Gln Leu Glu Asn Tyr Cys Asn
5
10
15
21
S
S
S
S
B
Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Pro Lys Ala
5
10
15
20
25
30
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.
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.
具有部分双键的性质
Has partial double bond character
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.
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. Hbond 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
N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
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基团分布在螺旋的表面
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-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.
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
以前称为超二级结构
Formerly known as supersecondary 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.
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
N端
C端
木瓜蛋白酶
小片段
323个氨基酸
5  核酸外切酶活性
大片段
/ Klenow 片段
604个氨基酸
DNA聚合酶活性
  5 核酸外切酶活性
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.
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.
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.