Cell Biology BIOL 3030 – Lecture 8: Protein Sorting I

Vocabulary flashcards covering key terms, molecules, sequences, pathways, and quality-control mechanisms involved in targeting proteins to and across the ER membrane as presented in Lecture 8 of BIOL 3030.

Protein Sorting

The cellular processes that direct newly made proteins to their correct destinations inside or outside the cell.

Signal-Based Targeting

Protein localization mechanism that relies on short amino-acid sequences (signals) and their receptors to move proteins into specific organelles or membranes.

Vesicle-Based Trafficking (Secretory Pathway)

Transport route whereby membrane-bound vesicles move proteins and lipids from the ER through the Golgi to the plasma membrane, lysosome, or secretion.

Endoplasmic Reticulum (ER)

An interconnected membrane network where lipid synthesis, calcium storage, and synthesis of secretory and membrane proteins occur.

Smooth ER (SER)

ER region lacking ribosomes; performs fatty acid & phospholipid synthesis and detoxification reactions, especially in liver cells.

Rough ER (RER)

ER domain studded with ribosomes; site of co-translational insertion of membrane, secretory, Golgi, and lysosomal proteins.

Cotranslational Translocation

Simultaneous synthesis and ER import of a nascent polypeptide through the translocon while it is still attached to the ribosome.

Signal Recognition Particle (SRP)

Cytosolic ribonucleoprotein that binds the ER signal sequence, pauses translation, and guides the ribosome-nascent chain complex to the ER membrane.

SRP Receptor

ER membrane protein that binds SRP–ribosome complexes and, with GTP hydrolysis, transfers them to the translocon.

ER Signal Sequence

N-terminal, ~20-aa hydrophobic segment acting as an address label for targeting ribosome translation complexes to the ER.

Translocon (Sec61 Complex)

Protein-conducting channel in the ER membrane that opens to allow nascent chains to enter the lumen or integrate into the bilayer.

Signal Peptidase

ER-resident enzyme that cleaves the ER signal sequence from many soluble proteins after they enter the lumen.

Stop-Transfer Anchor (STA) Sequence

Hydrophobic segment that halts translocation and becomes a transmembrane α-helix anchoring the protein in the ER membrane.

Signal-Anchor (SA) Sequence

Internal hydrophobic sequence that acts both as an ER targeting signal and as a transmembrane domain determining protein orientation.

Type I Membrane Protein

Single-pass protein with N-terminus in the lumen/extracellular space and a cleaved signal sequence followed by an STA segment.

Type II Membrane Protein

Single-pass protein whose internal SA positions the N-terminus in the cytosol; orientation influenced by flanking positive charges.

Type III Membrane Protein

Single-pass protein with C-terminal positive charges that force the N-terminus into the lumen; uses an internal SA.

Type IV Membrane Protein

Multi-pass protein containing multiple SA and STA sequences; spans the membrane several times (e.g., transporters, channels).

Tail-Anchored Protein

Protein with a single C-terminal transmembrane helix inserted post-translationally into the ER by the GET (Get3) pathway.

GET Pathway (Get3, Get1/2)

ATP-dependent system that delivers tail-anchored proteins to the ER membrane via Get3 chaperone and Get1/2 receptors.

Topogenic Sequences

Collective term for signal sequences, SA segments, and STA segments that determine protein insertion and orientation in membranes.

Glycosylation

Enzymatic addition of carbohydrate chains to proteins; enhances folding, stability, and cell–cell recognition.

O-Linked Oligosaccharide

Short sugar chain attached to serine or threonine residues mainly in the Golgi apparatus.

N-Linked Oligosaccharide

Branched sugar chain attached to asparagine within the motif Asn-X-Ser/Thr in the ER; begins as a 14-residue core.

Dolichol Phosphate

Long-chain lipid carrier that anchors the growing oligosaccharide precursor used for N-linked glycosylation in the ER membrane.

Oligosaccharyl Transferase

ER membrane enzyme that transfers the pre-assembled oligosaccharide from dolichol to the asparagine residue of a nascent chain.

Protein Disulfide Isomerase (PDI)

Luminal enzyme that catalyzes formation and rearrangement of disulfide bonds, aiding proper folding of secretory proteins.

Calnexin

Membrane-bound ER chaperone that binds monoglucosylated N-glycans to retain and fold glycoproteins.

Calreticulin

Soluble ER chaperone similar to calnexin; assists folding of glycoproteins by binding monoglucosylated N-glycans.

BiP (Binding Immunoglobulin Protein)

ER-resident Hsp70 chaperone that binds nascent polypeptides, prevents aggregation, and drives post-translational translocation.

ER Quality Control

Surveillance system ensuring only properly folded proteins exit the ER; misfolded ones are retained, reglucosylated, or degraded.

Unfolded Protein Response (UPR)

Signal pathway activated by accumulation of unfolded proteins in the ER, inducing transcription of chaperones and folding enzymes.

GPI Anchor (Glycosylphosphatidylinositol)

Covalent lipid linkage added in the ER that tethers proteins to the outer leaflet of the plasma membrane, promoting mobility in lipid rafts.

Lipid Rafts

Cholesterol- and sphingolipid-rich membrane microdomains where GPI-anchored proteins preferentially concentrate.

Dislocation (ER-Associated Degradation, ERAD)

Process exporting misfolded ER proteins to the cytosol for ubiquitination and proteasomal degradation.

Hydropathy Plot

Graph of a protein's hydrophobicity versus residue position, used to predict transmembrane segments.

Glucosidase I & II

ER enzymes that trim glucose residues from N-linked oligosaccharides during folding and quality-control cycles.

ER α-Mannosidase

Luminal enzyme that removes mannose residues from misfolded glycoproteins, marking them for ERAD.

Protein Folding Catalysts

Collective term for ER enzymes (PDI, peptidyl-prolyl isomerases, chaperones) that accelerate correct protein folding.

Secretory Pathway

Route beginning at the RER and proceeding through the Golgi to deliver soluble and membrane proteins to their final destinations.