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 \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 mitochondrialproteins are synthesized as cytosolic precursors containing uptake peptide
signals.Cytosolicchaperones deliver preproteins to channel linked receptors in the mitochondrial 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 chaperones) to the TIM23 or 22 (Translocase of Inner Membrane) at the inner membrane. Within the matrix the targeting sequence is cleaved off by mtHsp70. Three mitochondrial outer membrane receptors 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（其也充当分子伴侣）的送。内矩阵的靶向序列通过
TIM
TIM23或22（内膜的移位）的间空间输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 diameter 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。在基体一侧，发现结合
mtHsp70。
TIM44势必
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.
Proteintargeting靶向蛋白讲解(20201005143805)
