Biochemistry: Protein Translocation Types & Forms

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Table of Contents

Introduction
Types of proteins
Heteromeric channels
Forms of protein translocation
Cotranslational translocation
Posttranslational translocation
Eubacterial Posttranslational translocation
Conclusion
References

Introduction

Protein translocation is the process in which fully synthesized proteins are transported to the target organelle within the cell. This occurs via the heteromeric conduits of the Endoplasmic reticulum. Protein translocation is significant because it enhances the transportation of specific proteins to target organelles. Types of protein translocation processes include cotranslational translocation in addition to posttranslational translocation. This process takes place in different ways depending type of organism that is eukaryotes and prokaryotes as well as the type of proteins being translocated (Halic, 2005).

Types of proteins

There are two types of proteins; this includes secretory proteins as well as membrane proteins. Each type of protein has a different targeting signal, for example, cleavable signals target secretory proteins and this causes the proteins to cross the membrane completely. On the other hand, non-cleaved signals target membrane proteins. Non-cleaved signals are also known as transmembrane (TM) segments. The eventual result of this is the integration of TM segments within the lipid bilayer (Halic, 2005).

Heteromeric channels

The two types of proteins use protein-conducting channels in order for translocation to take place. The occurrence of this channel occurs due to the existence of a preserved heteromeric membrane protein complex. In prokaryotes, this complex is referred to as secY while in eukaryotes it is referred to as sec61. Components of this complex include three subunits namely a, g as well as b-subunits. Each type of subunit has a unique spanning pattern. For example, a-subunit spins within the complex ten times while both g and b-subunits spin within the complex once (Irihmovitch, 2003).

The heteromeric channel has a hydrophilic interior as well as a flexible pore. This allows the passage of large chemicals linked to amino acid side chains. Despite this flexibility, this path remains a barrier as the translocation process takes place thus preventing the passage of ions as well as miniature molecules. Another property heteromeric channel is its ability to open laterally. This allows lateral movement of transmembrane proteins from the hydrophilic environment to the outer hydrophobic layer of the lipid bilayer. The capability of the heteromeric channel to open in two different ways i.e., laterally and across discerns it from other conduits. Heteromeric channels have pores with dimensions ranging from 5–8 A° due to the small size of pores, a mechanism is needed to allow the further opening to facilitate the passing through of large polypeptide chain molecules. This mechanism occurs through lateral dislodgment of helices, which, attaches the pores residues. This property allows the pores to be flexible thus allowing movement of both small and large molecules through (Irihmovitch, 2003).

Forms of protein translocation

Since the sec61 and secY heteromeric channel is a reflexive pore, it allows polypeptide chains to slide back and forth. This necessitates a driving force that allows protein translocation. This is achieved through associations between the channel and various partners. Due to different partners, translocation is divided into three modes namely cotranslational, translocation, posttranslational translocation as well as eubacteria posttranslational translocation (Lurink & Sinning 2004).

Cotranslational translocation

In this form of translocation, the heteromeric channel associates Marjory with the ribosome. This is the most common type of protein translocation and occurs in all classes of organisms as well as cells. Cotranslational translation is responsible for integration between membrane proteins. The first phase of cotranslational translocation is the targeting phase. In this step, a signal recognition particle (SRP) directs a growing ribosome chain into the membrane. The ribosome has an SRP receptor, which also participates in the targeting phase (Halic &Beckmann 2005).

The second phase entails the binding of the ribosome to the heteromeric channel. Upon binding, the growing polypeptide is uncoupled from the ribosome to the heteromeric channel. The movement of the polypeptide chain across the heteromeric channel is facilitated by hydrolysis of GTP. GTP hydrolysis provides the needed energy to drive the proteins or polypeptide chain in a forward direction across the heteromeric channel. In case the ribosome produces a cytosolic sphere of membrane proteins, the protein is translocated laterally along the channel. Eventually, it emerges from heteromeric channel-ribosome junction askew into the cytosol (Mothes et al. 1997).

Posttranslational translocation

This mode of translocation occurs in eukaryotes where polypeptide chains or proteins are translocated after they are fully synthesized. In this mode of translocation, SRP interactions with polypeptide chains during protein synthesis do not exist because proteins translocated by this mode have a minimal hydrophobic signal sequence (Ng et al. 1996).

Posttranslational translocation has been studied and observed in S. cerevisiae and from this observation; the process is similar in higher prokaryotes. In posttranslational translocation, the heteromeric channel partners with luminal BiP protein to produce the driving force. Lumenal BiP proteins belong to Hsp70 class of ATPases. Posttranslational translocation’s driving energy is produced through the ratcheting mechanism. The binding of a polypeptide chain or protein with BiP proteins within the ER lumen prevents the polypeptide chain from sliding backside into the cytosol. The result of this is forward translocation movement (Matlack et al. 1999).

BiP protein is linked with ATP and has a peptide-binding pocket, which, aids in interaction with the Sec63p Lumenal domain. This association causes hydrolysis of ATP leading to the production of energy, which aids in the forward translocation of proteins within the heteromeric channel. Apart from ATP hydrolysis, this association causes closure of peptide–binding pocket thus preventing detachment of proteins being translocated. After the polypeptide has moved a considerable distance, it is received and bounded by another BiP protein molecule and the process goes on and on leading to frontward movement until the polypeptide chain transverses the channel. Release of BiP proteins from the polypeptide-binding pocket occurs after ATP replaces ADP. This allows a second polypeptide chain to be translocated and the process goes on and on. The ratcheting mechanism has some special aspects; this includes the loss of bound cytosolic chaperones by the polypeptide chains before translocation. The essence of this is to facilitate the forward movement of polypeptide chains. Before translocation, fully synthesized proteins are bound to various types of chaperones bind the polypeptide chains specifically at the C-terminus however; upon binding of polypeptide chain with Sec complex via the N-terminal sequences, a chaperone is released (Plath & Rapoport. 2000).

Eubacterial Posttranslational translocation

This type of protein translocation occurs only in eubacteria and is meant for secretory proteins. The heteromeric partner, in this case, is cytosolic ATPase known as SecA. SecA enhances the forward movement of polypeptide chains along the heteromeric channel. Since this type of translocation occurs in prokaryotes such as eubacteria, the heteromeric channel, in this case, is SecY. SecA proteins undergo assenting changes after binding with the polypeptide chain. Some organisms such as Archaea display both cotranslational as well as posttranslational translocation mechanisms. Despite the existence of the two translocation mechanism, it is uncertain how they carry out posttranslational translocation because they lack Sec62/63 as well as SecA complexes (Mori & Ito 2000).

Conclusion

Protein translocation occurs across the endoplasmic reticulum through heteromeric channels to target organelles; protein translocation modes include cotranslational and posttranslational translocation. This depends on the type of protein and type of organism. This process enhances the transportation of specific proteins to the specific organelle. This is enhanced by a specific amino acid sequence, which occurs at the end of each protein. The amino acid sequence acts as a code that directs the protein to a specific organelle. Errors associated with protein translocation lead to the occurrence of genetic diseases, therefore, the discovery of this process has enabled scientists to explain the occurrence of various disorders.

References

Economou A, Wickner W. 1994. SecA promotes preprotein translocation by undergoing ATPdriven cycles of membrane insertion and deinsertion. Cell 78:835–43.

Halic M, Beckmann R. 2005. The signal recognition particle and its interactions during protein targeting. Curr. Opin. Structure. Biol. 15:116–25.

Irihmovitch V, Eichler J. 2003. Post-translational secretion of fusion proteins in the halophilic archaea Haloferax volcanii. J. Biol. Chem. 278:12881–87.

Matlack KES, MothesW, RapoportTA. 1998. Protein translocation: tunnel vision. Cell 92:381–390.

Mori H, Ito K. 2001. The Sec protein-translocation pathway. Trends Microbiol. 9:494–500.

Ng DT, Brown JD, Walter P. 1996. Signal sequences specify the targeting route to the endoplasmic reticulum membrane. J. Cell Biol. 134:269–78.

Plath K, Rapoport TA. 2000. Spontaneous release of cytosolic proteins from posttranslational substrates before their transport into the endoplasmic reticulum. J. Cell Biol. 151:167–78.

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