Proteintargeting靶向蛋白讲解

Protein targeting
From Wikipedia, the free encyclopedia
This article deals with protein targeting in eukaryotes except where noted.
Protein targeting or protein sorting is the biological mechanism by which proteins are transported to the appropriate destinations in the cell or outside of it. Proteins can be targeted to the inner space of
an organelle, different intracellular membranes, plasma membrane, or to exterior of the cell via secretion. This delivery process is carried out based on information contained in the protein itself. Correct sorting is crucial for the cell; errors can lead to diseases.
靶向蛋白
维基百科，自由的百科全书
这篇文章除了注意的地方在真核生物蛋白靶向交易。

蛋白靶向或蛋白质排序是通过该蛋白质运输到细胞中的相应的目
的地或它的外部的生物机制。

蛋白质可靶向至细胞器，不同细胞
内膜，质膜的内部空间，或通过分泌细胞的外部。

这个输送过程
是基于包含在该蛋白质本身的信息进行的。

正确的排序是细胞的
关键;错误可以导致疾病的发生。

Targeting signals
Targeting signals are the pieces of information that enable the cellular transport machinery to correctly position a protein inside or outside the cell. This information is contained in the p olypeptide
chain or in the folded protein. The continuous stretch of amino
acid residues in the chain that enables targeting are called signal peptides or targeting peptides. There are two types of targeting
. The peptides, the p resequences and the internal targeting peptides presequences of the targeting peptide are often found at the
N-terminal extension and is composed of between 6-136 basic and hydrophobic amino acids. In case of peroxisomes the targeting sequence is on the C-terminal extension mostly. Other signals, known as signal patches, are composed of parts which are separate in
the primary sequence. They become functional when f olding brings them together on the protein surface. In addition, protein modifications like glycosylations can induce targeting.
靶向信号
定位信号是使蜂窝运输机械正确定位内或细胞外的蛋白质的
信息块。

此信息包含在该多肽链，或在折叠的蛋白质。

的链中的
氨基酸残基使得能够针对连续拉伸称为信号肽或靶向肽。

有两种
类型的靶向肽的前序列和内部靶向肽。

所述靶向肽的前序列常常
发现在N-端延伸，并6-136基本和疏水氨基酸之间组成。

在过氧
化物酶的情况下，靶向序列是在C-末端延伸居多。

其他信号，称
为信号贴剂，是由它们在一级序列分开的零件。

当折叠使他们在
一起蛋白质表面上他们变得功能。

此外，像糖基化蛋白修饰可诱
发靶向。

Protein translocation
In 1970, Günter Blobel conducted experiments on the translocation of proteins across membranes. He was awarded the 1999 Nobel prize for his findings. He discovered that many proteins have a s ignal sequence, that is, a short a mino acid sequence at one end that functions like a postal code for the target organelle.
The translation of mRNA into protein by a ribosome takes place within the cytosol. If the synthesized proteins "belong" in a different organelle, they can be transported there in either of two ways depending on the protein: C o-translational translocation (translocation during the process of translation), and Post-translational translocation (translocation after the process of translation is complete).
蛋白质易位
在1970年，古特·布洛伯尔上跨膜蛋白的易位进行的实验。

他被授予1999年诺贝尔文学奖，他的研究结果。

他发现，许多蛋
白具有信号序列，也就是说，在一端具有短的氨基酸序列，像对
靶细胞器邮政编码功能。

mRNA的核糖体翻译成蛋白质发生细胞
质内进行。

共翻译转运（易位翻译的过程中），和翻译后转运（处
理之后易位：如果合成的蛋白质“属于”在不同的细胞器，它们
可以有以下两种方式取决于蛋白质上运翻译完成）。

Co-translational translocation
Most proteins that are secretory, membrane-bound, or reside in the endoplasmic reticulum (ER), golgi or endosomes use the
co-translational translocation pathway. This process begins with the
N-terminal signal peptide of the protein being recognized by a signal recognition particle (SRP) while the protein is still being synthesized on the ribosome. The synthesis pauses while the ribosome-protein complex is transferred to an S RP receptor on the ER in eukaryotes,
and the plasma membrane in prokaryotes. There, the nascent protein is inserted into the translocon, a membrane-bound protein conducting channel composed of the Sec61 translocation complex in eukaryotes, and the homologous S ecYEG complex in prokaryotes. In secretory proteins and type I transmembrane proteins, the signal sequence is immediately cleaved from the nascent polypeptide once it has been translocated into the membrane of the ER (eukaryotes) or plasma membrane (prokaryotes) by s ignal peptidase. The signal sequence of type II membrane proteins and some membrane proteins are not cleaved off and therefore are referred to as signal anchor sequences. Within the ER, the protein is first covered by a c haperone protein to protect it from the high concentration of other proteins in the ER,
giving it time to fold correctly. Once folded, the protein is modified as needed (for example, by g lycosylation), then transported to the Golgi for further processing and goes to its target organelles or is retained in the ER by various ER retention mechanisms.
共翻译转运
是分泌大多数蛋白，膜结合，或驻留在内质网（ER），高尔基体或内体使用共翻译转运途径。

此过程开始于该蛋白的N-末端信号肽由信号识别颗粒（SRP）所识别，而蛋白质仍在核糖体上合成的。

而核糖体蛋白复合物被转移到在真核生物内质网的SRP受体，并在原核生物质膜合成暂停。

那里，初生蛋白插入位子，在真核
生物的Sec61易位复合物组成的膜结合蛋白导电通道，而在原核
生物同源SecYEG复杂。

在分泌蛋白和I型跨膜蛋白，信号序列
被立即从新生多肽裂解一旦已转运到内质网（真核生物）或质膜
（原核生物）由信号肽酶的膜。

II型膜蛋白和一些膜蛋白的信号
序列不裂解，因此作为信号锚定序列被称作。

内质网，蛋白质首
先被伴侣蛋白覆盖，以保护其免受在ER其它蛋白质的高浓度，给它的时间来正确地折叠。

一旦折叠，蛋白质根据需要修改（例如，
通过糖基化），然后运到高尔基体进行进一步的处理，然后进到
它的靶细胞器或保持在通过各种ER滞留机制对ER
The amino acid chain of t ransmembrane proteins, which often
are transmembrane receptors, passes through a membrane one or several times. They are inserted into the membrane by translocation,
until the process is interrupted by a stop-transfer sequence, also called a membrane anchor sequence. These complex membrane proteins are at the moment mostly understood using the same model of targeting that has been developed for secretory proteins. However, many complex multi-transmembrane proteins contain structural aspects that do not fit the model. Seven transmembrane G-protein coupled receptors (which represent about 5% of the genes in humans) mostly do not have an amino-terminal signal sequence. In contrast to secretory proteins, the first transmembrane domain acts as the first signal sequence, which targets them to the ER membrane. This also results in the translocation of the amino terminus of the protein into
the ER membrane lumen. This would seem to break the rule of
"co-translational" translocation which has always held for mammalian proteins targeted to the ER. This has been demonstrated
with opsin with in vitro experiments.[1][2] A great deal of the mechanics of transmembrane topology and folding remains to be elucidated.
跨膜蛋白，这往往是跨膜受体的氨基酸链，穿过膜一次或几次。

它们被插入由易位膜，直到该过程被停止传送序列中断，也称为
膜锚定序列。

这些复杂膜蛋白的时刻使用已经为分泌蛋白开发定
位的相同的模型大多理解。

然而，许多复杂的多跨膜蛋白包含不
适合该模型结构方面。

七跨膜G蛋白偶联受体（其代表的基因的
约5％的人）大多不具有氨基末端信号序列。

在对比分泌蛋白，所述第一跨膜结构域作为第一信号序列，其它们靶向到内质网膜。

这也导致了蛋白质的氨基末端到ER膜腔的易位。

这似乎打破一向
举行有针对性的ER哺乳动物蛋白“合作翻译”易位的统治。

这已被证实与在体外实验中视蛋白。

[1] [2]的跨膜拓扑结构和折叠的机
制大量尚待阐明。

Post-translational translocation
Even though most secretory proteins are co-translationally translocated, some are translated in the cytosol and later transported to the ER/plasma membrane by a post-translational system. In prokaryotes this requires certain cofactors such as SecA and SecB.
This pathway is poorly understood in eukaryotes, but is facilitated
by Sec62 and Sec63, two membrane-bound proteins.
In addition, proteins targeted to other destinations, such
as mitochondria, chloroplasts, or peroxisomes, use specialized
post-translational pathways. Also, proteins targeted for the nucleus are translocated post-translation. They pass through the nuclear
envelope via nuclear pores.
翻译后转运
尽管大多数分泌蛋白被共翻译转运，一些被转换在胞质溶胶
中，后来由翻译后系统输送到ER /质膜。

在原核生物中这需要一
定的辅助因子，如SecA的和的SecB。

这个途径是知之甚少在真
核生物中，但由Sec62和Sec63两个膜结合蛋白促进。

此外，蛋白质定位到其他目的地，例如线粒体，叶绿体或过氧
化物酶体，使用专门的翻译后通路。

此外，针对细胞核蛋白易位
后的翻译。

他们通过通过核孔核膜。

Sorting of proteins to mitochondria
Most mitochondrial proteins are synthesized
as cytosolic precursors containing uptake peptide
signals.Cytosolic chaperones deliver preproteins to channel linked receptors in the m itochondrial membrane. Thepreprotein with presequence targeted for the mitochondria is bound by receptors and the General Import Pore (GIP) (Receptors and GIP are collectively known as Translocase of Outer Membrane or TOM) at the outer membrane. The preprotein is translocated through TOM as hairpin loops. The preprotein is transported through the intermembrane space by small TIMs (which also acts as molecular c haperones) to the TIM23 or 22 (Translocase of Inner Membrane) at the i nner membrane. Within the matrix the targeting sequence is cleaved off by mtHsp70. Three mitochondrial outer membrane r eceptors are known: TOM20, TOM22 and TOM70
蛋白质排序到线粒体
大多数线粒体蛋白质被合成作为含有摄取肽signals.Cytosolic伴侣胞质前体递送preproteins到信道连接的受体在线粒体膜。

与前序
列针对线粒体Thepreprotein通过受体结合和常规导入孔（GIP）的外膜（受体和GIP被统称为外膜或TOM的移位）。

该前蛋白是通过TOM易位的发夹环。

该前蛋白通过由在其内的膜小的TIM （其也充当分子伴侣）的TIM23或22（内膜的移位）的间空间输送。

内矩阵的靶向序列通过mtHsp70切除。

三线粒体外膜受体是已知的：TOM20，TOM22和TOM70
TOM70: Binds to internal targeting peptides and acts as a docking point for cytosolic chaperones.
TOM20: Binds presequences
TOM22: Binds both presequences and internal targeting peptides The TOM channel (TOM40) is a cation specific high conductance channel with a molecular weight of 410 kDaand a pore d iameter of 21?.
The presequence translocase23 (TIM23) is localized to the mitochondial inner membrane and acts a pore forming protein which binds precursor proteins with its N-terminus. TIM23 acts a translocator for preproteins for the mitochondrial matrix, the inner mitochondrial membrane as well as for the intermembrane space. TIM50 is bound to TIM23 at the inner mitochondrial side and found
to bind presequences. TIM44 is bound on the matrix side and found binding to mtHsp70.
TOM70：绑定到内部靶向肽和充当停靠点为胞质分子伴侣。

TOM20：前序列绑定
TOM22：既绑定前序列和内部靶向肽
的TOM通道（TOM40）是具有410分子量的阳离子特定高电导
通道kDaand21a的孔径。

的前序列translocase23（TIM23）被定位于mitochondial内膜和充当其结合的前体蛋白，其N末端的孔形成蛋白。

TIM23充当为preproteins为线粒体基质，内线粒体膜以及用于间空间一转运。

TIM50势必TIM23在线粒体侧，发现绑定前序列。

TIM44势必
在基体一侧，发现结合mtHsp70。

The presequence translocase22 (TIM22) binds preproteins exclusively bound for the inner mitochondrial membrane.
Mitochondrial matrix targeting sequences are rich in positively charged amino acids and hydroxylated ones.
Proteins are targeted to submitochondrial compartments by multiple signals and several pathways.
Targeting to the outer membrane, intermembrane space, and inner membrane often requires another signal sequence in addition to the matrix targeting sequence.
该前序列translocase22（TIM22）结合专开往线粒体内膜preproteins。

线粒体基质靶向序列中富含正电荷的氨基酸和羟基化的。

蛋白质是有针对性地submitochondrial由多个信号和几个途径车
厢。

靶向外膜，间空间，和内膜通常需要除了基质靶向序列的另一信
号序列。

Sorting of proteins to chloroplasts
The preprotein for chloroplasts may contain a stromal import sequence or a stromal and thylakoid targeting sequence. The majority of preproteins are translocated through the Toc and Tic complexes located within the chloroplast envelope. In the stroma the stromal import sequence is cleaved off and folded as well as intra-chloroplast sorting to thylakoids continues. Proteins targeted to the envelope of chloroplasts usually lack cleavable sorting sequence.
蛋白质排序叶绿体
叶绿体的前蛋白可能含有间质导入序列或间质类囊体和靶向
序列。

多数preproteins都是通过TOC和位于叶绿体壳内抽动络合
物易位。

在基质的基质导入序列被切除并折叠以及帧内叶绿体分
拣到类囊体继续。

针对叶绿体的包膜蛋白通常缺乏裂解的排序顺
序。

Sorting of proteins to both chloroplasts and mitochondria Many proteins are needed in both mitochondria and chloroplasts.
In general the targeting peptide is of intermediate character to the two specific ones. The targeting peptides of these proteins have a high content of basic and h ydrophobic amino acids, a low content of negatively charged a mino acids. They have a lower content of alanine and a higher content of leucine and phenylalanine. The dual targeted proteins have a more hydrophobic targeting peptide than both mitochondrial and chloroplastic ones.
蛋白质的分拣既叶绿体和线粒体
许多蛋白中需要两个线粒体和叶绿体。

在一般的靶向肽是中间
字符到两个特定的人的。

这些蛋白质的靶向肽具有的基本的和疏
水性氨基酸含量较高，带负电荷的氨基酸的含量低。

它们具有丙
氨酸的含量较低和亮氨酸和苯丙氨酸的含量较高。

双重靶向蛋白
质具有比两个线粒体和叶绿体那些更疏水的靶向肽。

Sorting of proteins to peroxisomes
All peroxisomal proteins are encoded by nuclear genes.
To date there are two types of known Peroxisome Targeting
Signals (PTS):
Peroxisome targeting signal 1 (PTS1): a C-terminal tripeptide with a consensus sequence (S/A/C)-(K/R/H)-(L/A). The most common PTS1
is serine-lysine-leucine (SKL). Most peroxisomal matrix proteins possess a PTS1 type signal.
Peroxisome targeting signal 2 (PTS2): a nonapeptide located near the N-terminus with a consensus sequence
(R/K)-(L/V/I)-XXXXX-(H/Q)-(L/A/F) (where X can be any amino acid).
There are also proteins that possess neither of these signals. Their transport may be based on a so-called "piggy-back" mechanism: such proteins associate with PTS1-possessing matrix proteins and are translocated into the peroxisomal matrix together with them.
蛋白质排序过氧化物酶体
所有的过氧化物酶体蛋白由核基因编码的。

迄今有两种类型的已知的过氧化物酶体靶向信号（PTS）的：
过氧化物酶体定位信号1（PTS1）：C-末端三肽具有共有序列（S / A / C）- （K/ R/ H）- （L/ A）。

最常见的PTS1为丝氨酸- 赖氨酸- 亮氨酸（SKL）。

大多数过氧化物酶体基质蛋白拥有PTS1类型的信号。

过氧化物酶体靶向信号2（PTS2）：位于N末端具有共有序列附
近的九肽（R / K）- （L / V/ I）-XXXXX-（H / Q）- （L / A / F）（其中X可以是任何氨基酸）。

还有一些既没有这些信号的蛋白质。

它们的运输可基于所谓的“背驮式”机制：这些蛋白质关联与PTS1-具有基质蛋白和与它们一
起转移进入过氧化物酶体基质。

Diseases
Peroxisomal protein transport is defective in the following genetic diseases:
Zellweger syndrome.
Adrenoleukodystrophy (ALD).
Refsum disease
Protein targeting in bacteria and archaea
As discussed above (see protein translocation), most prokaryotic membrane-bound and secretory proteins are targeted to the plasma membrane by either a co-translation pathway that uses bacterial SRP or a post-translation pathway that requires SecA and SecB. At the plasma membrane, these two pathways deliver proteins to the SecYEG translocon for translocation. Bacteria may have a single plasma membrane (G ram-positive bacteria), or an inner membrane plus an outer membrane separated by the periplasm (Gram-negative bacteria). Besides the plasma membrane the majority of prokaryotes lack membrane-bound organelles as found in eukaryotes, but they
may assemble proteins onto various types of inclusions such as gas vesicles and storage granules.
疾病
过氧化物酶体蛋白转运是在下面的遗传性疾病缺陷：
?齐薇格综合征。

?肾上腺脑白质营养不良（ALD）。

?雷弗素姆病
蛋白质在细菌和古细菌靶向
如上所讨论的（参见蛋白易位），大多数原核生物膜结合和分
泌蛋白由任一使用的细菌的SRP或需要SecA的和的SecB一个翻
译后途径的共翻译途径靶向到质膜。

在质膜，这两种途径递送蛋
白质的SecYEG位子为易位。

细菌可以具有单质膜（革兰氏阳性菌），或内膜加由周质（革兰氏阴性细菌）中分离的外膜。

除了
质膜大多数原核生物的缺乏膜结合细胞器如在真核生物中发现
的，但它们可以聚集蛋白到各种类型的夹杂物如气体囊泡和存储
颗粒。

Gram-negative bacteria
Main article: Gram-Negative Bacterial Secretion
In gram-negative bacteria proteins may be incorporated into the plasma membrane, the outer membrane, the periplasm or secreted into。