moving proteins into membranes & organelles

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Questions and Answers

What is the role of the nuclear-localization signal (NLS) in protein import?

It prevents proteins from entering the endoplasmic reticulum.

It functions to export proteins out of the nucleus.

It directs the translocation of proteins into the nucleus. (correct)

It serves as a marker for cytoplasmic degradation.

What does the process of importing proteins into the nucleus involve?

Fusion with the nuclear membrane.

Using vesicles to transport proteins directly.

Binding to nuclear export signals.

Interaction with importins and nucleoporins. (correct)

Which statement about importins is accurate?

They are recycled after releasing their cargo in the cytoplasm. (correct)

They can only transport proteins without a nuclear-localization signal.

They bind cargo proteins for export out of the nucleus.

They are not involved in the import of RNA or ribosomal subunits.

What effect does the interaction with Ran-GTP have on importins?

It causes a conformational change leading to cargo release. Signup and view all the answers

Which of the following molecules is NOT typically exported from the nucleus using a similar mechanism to protein import?

Proteins containing nuclear-localization signals Signup and view all the answers

What role does Ran-GTP play in the export of proteins from the nucleus?

It binds to exportin and cargo proteins during the export process. Signup and view all the answers

Which of the following statements about NLS and NES in proteins is correct?

Proteins must possess both NLS and NES to shuttle between nucleus and cytoplasm. Signup and view all the answers

What is the function of GEF in the GTP switch mechanism?

It mediates the exchange of GDP for GTP to activate proteins. Signup and view all the answers

What is the role of GAP in the transport mechanism of GTP switch proteins?

It accelerates the hydrolysis of GTP to GDP, turning off the protein. Signup and view all the answers

How does the exportin-cargo complex exit the nucleus through the nuclear pore complex (NPC)?

Via interactions with nucleoporins during complex diffusion. Signup and view all the answers

What primarily distinguishes proteins undergoing signal-based targeting from those in vesicle-based trafficking?

Signal-based targeting relies on amino acid sequences. Signup and view all the answers

Which of the following components is essential for the nonsecretory pathway of protein sorting?

Localization to peroxisomes or mitochondria. Signup and view all the answers

What is the role of the signal sequence in protein targeting?

It encodes information for organelle localization. Signup and view all the answers

In which pathway are proteins destined for export from the cell synthesized?

Secretory pathway Signup and view all the answers

What mechanism couples the translocation of proteins across membranes?

Energetically favorable process Signup and view all the answers

Which statement about the secretory pathway is true?

It includes protein transport to lysosomes. Signup and view all the answers

What occurs after a receptor binds to a signal sequence during protein sorting?

The protein is transferred through a translocation channel. Signup and view all the answers

Which of these is NOT a destination for proteins synthesized on free ribosomes?

Golgi apparatus Signup and view all the answers

What is the consequence of the mutation in AAT?

It folds improperly and destroys elastin Signup and view all the answers

What is the primary difference between the nonsecretory and secretory pathways in protein sorting?

The nonsecretory pathway involves free ribosomes, while the secretory pathway involves bound ribosomes. Signup and view all the answers

Which process is primarily responsible for the degradation of misfolded proteins?

Ubiquitin/proteasome pathways Signup and view all the answers

What is the requirement for protein translocation into mitochondria?

Active mitochondrial respiration Signup and view all the answers

What role do targeting sequences play in protein sorting?

They provide the information needed to target proteins to particular organelles. Signup and view all the answers

How are peroxisomal proteins typically imported into peroxisomes?

They are imported in a folded state Signup and view all the answers

Which energy source is commonly involved in the translocation of proteins across membranes?

ATP Signup and view all the answers

What is the role of the targeting sequence called MTS in mitochondrial protein import?

To assist in membrane translocation Signup and view all the answers

Which organelles are primarily associated with the nonsecretory pathway of protein sorting?

Peroxisomes, mitochondria, and nucleus Signup and view all the answers

What motif is contained in the PTS1 used for peroxisomal targeting?

Serine-Lysine-Leucine Signup and view all the answers

What feature characterizes the receptors that bind targeting sequences?

They are specific and bind to only one type of signal sequence. Signup and view all the answers

Which of the following pathways involves proteins localized to the cytosol?

Nonsecretory pathway Signup and view all the answers

What type of protein structure is required for mitochondrial import?

Unfolded protein Signup and view all the answers

Which chaperone is required to maintain the unfolded state of proteins for mitochondrial import?

Hsc70 Signup and view all the answers

What is the significance of the amino acid sequence of targeting sequences in protein sorting?

It encodes information for specific organelle localization. Signup and view all the answers

In the context of protein sorting, what does the term 'vesicle-based trafficking' refer to?

The transport of proteins via lipid bilayer vesicles. Signup and view all the answers

What happens to the exportin-cargo complex after Ran-GTP hydrolysis?

It disassociates, and transporters are recycled. Signup and view all the answers

Which component is necessary for exportin to bind to the cargo protein?

Nuclear-export signal (NES) Signup and view all the answers

How does Ran protein contribute to the transport process between the nucleus and cytoplasm?

By switching between active and inactive states. Signup and view all the answers

What is the primary role of nucleoporins in the export process?

To facilitate the movement through the nuclear pore complex (NPC). Signup and view all the answers

In the context of GTP switch proteins, what triggers the conversion from inactive to active state?

Release of GDP by guanine nucleotide exchange factors (GEF). Signup and view all the answers

What is the primary impact of Zellweger syndrome on peroxisomes?

Defective peroxisomes leading to impaired protein transport Signup and view all the answers

Which organ systems are most severely affected by Zellweger syndrome?

Liver, kidneys, and brain Signup and view all the answers

What is a characteristic feature observed at birth in infants with Zellweger syndrome?

Unusual facial characteristics Signup and view all the answers

What is the mechanism of transport through the nuclear pore complexes (NPCs)?

Selective energy-dependent transport for molecules larger than 9nm Signup and view all the answers

What structures are included in the composition of a nuclear pore complex (NPC)?

Nucleoporin proteins and cytoplasmic filaments Signup and view all the answers

What role do FG nucleoporins play in nuclear transport?

They bind selectively to nuclear transporters Signup and view all the answers

Which of the following features does the nuclear transporters possess?

Long hydrophobic regions on their surface Signup and view all the answers

What is a common clinical manifestation of Zellweger syndrome in infants?

Severe jaundice Signup and view all the answers

What is the initial role of the ER signal sequence in targeting nascent secretory proteins?

It directs the ribosome to the ER membrane. Signup and view all the answers

Which components are essential for the process of co-translational translocation?

SRP, SRP receptor, and translocon Signup and view all the answers

For what type of proteins is post-translational translocation primarily used?

Some eukaryotic proteins after translation is complete Signup and view all the answers

What classification do Type II and Type III proteins share in terms of their N-terminus?

They both lack a cleavable N-terminus. Signup and view all the answers

Which of the following describes the Sec61 complex in relation to the translocon?

It closes when not bound to the SRP or ribosome complex. Signup and view all the answers

What is a significant characteristic of Type IV A proteins?

They are multi-pass proteins with segments spanning the membrane multiple times. Signup and view all the answers

Which modification is primarily associated with glycosylation in the ER?

Attachment of carbohydrates to serine, threonine, or asparagine Signup and view all the answers

How does the SRP facilitate the attachment of the ribosome to the ER membrane?

By binding to the ribosome and nascent protein. Signup and view all the answers

What is the role of the GTP-binding α subunit in the SRP receptor?

It aids the dissociation of the SRP complex after attachment. Signup and view all the answers

Which statement about chaperones in the ER is accurate?

They help ensure proper protein folding and prevent aggregation. Signup and view all the answers

Lipid-anchored proteins like GPI-linked proteins primarily differ from other membrane proteins in that they:

Do not possess transmembrane segments. Signup and view all the answers

Which of the following is crucial for the translocation of nascent proteins into the ER?

Cooperative binding of SRP and ribosome Signup and view all the answers

Which type of protein spans the membrane multiple times and typically includes ion channels?

Type IV A proteins Signup and view all the answers

Study Notes

Protein Sorting

Proteins are sorted and targeted to specific locations.
Two general processes are involved in protein sorting: signal-based targeting and vesicle-based trafficking.
For membrane proteins, targeting involves inserting the protein into the lipid bilayer.
For water-soluble proteins, targeting involves translocating the entire protein across the membrane into the aqueous interior of the organelle.

Targeting Mechanisms

Targeting information, encoded within the protein as a sequence of 20-50 amino acids, determines the destination of the protein.
These sequences are called targeting sequences, signal sequences, or signal peptides.
Each organelle has receptors that bind to specific signal sequences.
Once bound, the receptor then interacts with a translocation channel to move the protein across the membrane.

Key Considerations

Protein sorting is a complex process that involves understanding the signal sequence, its receptor, and the energy requirements of the process.
For export, exportins bind to proteins containing nuclear-export signals (NES) and move them out of the nucleus.
This process requires Ran, a G protein that switches between two conformations depending on whether it is bound to GTP or GDP.

The Nuclear Pore Complex (NPC)

The NPC acts as a selective gate allowing the passage of water-soluble molecules, but not larger macromolecules.
The NPC is made of multiple proteins, including nucleoporins.

Nuclear Import

Proteins destined for the nucleus contain a nuclear-localization signal (NLS), a short amino acid sequence that directs their translocation.
Importin, a transport protein, binds to the NLS and facilitates movement into the nucleus.
Once inside the nucleus, importin interacts with Ran-GTP, causing a conformational change that releases the cargo protein.

Nuclear Export

Similar to import, nuclear export involves specific protein sequences that signal export and utilizes transport proteins.
This system also relies on Ran-GTP for protein release from the transport complex.

GTP Switch Proteins

These proteins are involved in signal transduction.
GTP-bound proteins are "on" and GDP-bound proteins are "off".
GEF (guanine nucleotide exchange factors) facilitate the conversion from inactive to active state, and GAP (GTPase-activating proteins) accelerate the inactivation of the protein.

Protein Sorting

Cells use protein sorting to direct proteins to specific cellular compartments.
Protein sorting is important for maintaining cellular function and organization.
There are two general processes for protein sorting: signal-based targeting and vesicle-based trafficking.
Signal-based targeting uses signal sequences to direct proteins to specific locations.
Vesicle-based trafficking uses membrane-bound vesicles to transport proteins between compartments.

Non-Secretory Pathway

This pathway sorts proteins to organelles like the cytosol, peroxisomes, mitochondria, chloroplasts, and nucleus.
Proteins synthesized on free ribosomes are sorted by this pathway.

Secretory Pathway

This pathway sorts proteins synthesized on bound ribosomes to the ER, plasma membrane, Golgi apparatus, lysosomes, or for export from the cell.

Targeting Sequences

Targeting sequences, also known as signal sequences or signal peptides, are short sequences of amino acids that direct proteins to specific organelles.
These sequences bind to receptors on the organelle membrane, initiating protein translocation.
Different organelles have specific receptors that bind to unique signal sequences.

Co-translational Translocation

This process involves the translocation of a nascent polypeptide through the ER membrane as the protein is being synthesized.
It requires the involvement of the Signal Recognition Particle (SRP) and the SRP receptor on the ER membrane.

Signal Recognition Particle (SRP)

This particle is composed of RNA and six different polypeptides.
It recognizes and binds to the signal sequence of the nascent protein.
The SRP then interacts with the SRP receptor on the ER membrane, bringing the ribosome and nascent protein to the ER.

SRP Receptor

This protein is embedded in the ER membrane and consists of two subunits (α and β).
The α subunit interacts with the SRP and binds GTP.
The β subunit is anchored in the membrane.

Translocon

This is a protein complex that forms a translocation channel through the ER membrane.
It allows the signal sequence and the polypeptide to enter the ER lumen.
The signal sequence interacts with amino acids in the Sec61 complex (part of the translocon).

Post-translational Translocation

This process occurs after protein synthesis is complete.
It is used for proteins that enter the ER lumen after translation.
It involves the Sec61 translocon, Sec63 complex, and BiP (a chaperone protein).

Type I Proteins

These are single-pass transmembrane proteins with their N-terminus facing the exoplasmic face and C-terminus facing the cytosol.
They have a stop-transfer anchor sequence that stops translocation and inserts the protein into the membrane.

Type II Proteins

These are single-pass transmembrane proteins with their N-terminus facing the cytosol.
They have a signal-anchor sequence that acts as both an ER signal sequence and a membrane-anchor sequence.

Type III Proteins

These are single-pass transmembrane proteins with their N-terminus facing the exoplasmic face.
They have a signal-anchor sequence that acts as both an ER signal sequence and a membrane-anchor sequence.

Type IV Proteins

These are multi-pass transmembrane proteins.
They have multiple transmembrane domains.
Type IVA have their N-terminus facing the cytosol, while Type IVB have their N-terminus facing the exoplasmic face.

GPI-linked Proteins

These proteins are anchored to the membrane through a glycosylphosphatidylinositol (GPI) molecule.
They lack hydrophobic transmembrane domains.

Glycosylation

This is a major protein modification that involves the addition of carbohydrates to proteins.
There are two types of glycosylation: N-linked (addition to asparagine) and O-linked (addition to serine or threonine).
Glycosylation plays a role in protein folding, stability, and function.

Degradation of Misfolded Proteins

Misfolded proteins are exported through the translocon to the cytosol.
They are degraded by the ubiquitin/proteasome system.

Mitochondrial Import

Most mitochondrial proteins are synthesized on free ribosomes and imported from the cytosol.
They have a mitochondrial targeting sequence (MTS) at their N-terminus, which is cleaved in the matrix.
Import into the mitochondria requires ATP and a proton motive force.

Peroxisomal Proteins

These proteins are synthesized on free ribosomes and imported into peroxisomes.
They possess a peroxisomal targeting sequence (PTS) that can be either PTS1 (C-terminal) or PTS2 (N-terminal).
PTS1 typically contains an SKL (serine-lysine-leucine) motif.
Import into peroxisomes requires ATP and involves receptor proteins (Pex5 and Pex7).

Nuclear Pore Complex (NPC)

This complex allows molecules to enter and exit the nucleus.
It consists of nucleoporin proteins arranged in a structure with a central transporter.
Small molecules can passively diffuse through the NPC, while larger molecules require specific transporters.

Nuclear Localization Signal (NLS)

Proteins destined for the nucleus have a NLS that interacts with importins (nuclear import receptors).
Importins bind to the NLS and guide the protein through the NPC.

Nuclear Export Signal (NES)

Proteins destined for export from the nucleus contain an NES that interacts with exportins (nuclear export receptors).
Exportins bind to the NES and guide the protein through the NPC.

Ran

Ran is a GTP-binding protein that plays a role in both nuclear import and export.
It exists in different conformations depending on whether GTP or GDP is bound.

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Description

This quiz covers the processes involved in protein sorting, including signal-based targeting and vesicle-based trafficking. It examines how targeting sequences dictate protein destination and the interaction with organelle receptors. Test your understanding of these complex biological mechanisms.