Chapter 13: Moving Proteins into Membranes and Organelles

Vocabulary flashcards covering the targeting, membrane insertion, modification, folding, and quality control of proteins in the endoplasmic reticulum based on Molecular Cell Biology Chapter 13.

Rough Endoplasmic Reticulum (RER)

A subcompartment of the endoplasmic reticulum consisting of a network of flattened sacs (cisternae) studded with ribosomes on its cytosolic surface that functions in the synthesis of membrane, lysosomal, and secretory proteins.

Smooth Endoplasmic Reticulum (SER)

A subcompartment of the endoplasmic reticulum devoid of ribosomes that carries out the synthesis of membrane lipids (such as cholesterol) and steroid hormones, liver detoxification via cytochrome P450 enzymes, and calcium ion sequestration in muscle cells.

Polyribosome

A single mRNA molecule actively translated by multiple ribosomes simultaneously at various stages of polypeptide elongation.

Signal Recognition Particle (SRP)

A cytosolic ribonucleoprotein complex consisting of six proteins bound to a 300-nucleotide RNA scaffold that binds nascent ER signal sequences, halts translation, and targets the ribosome complex to the ER membrane.

P54 Subunit

The subunit of the signal recognition particle (homologous to bacterial Ffh) that features a hydrophobic binding groove lined with methionine residues to bind the hydrophobic core of ER signal sequences.

FtsY

The archaeal/bacterial homolog of the $\alpha$ subunit of the SRP receptor that binds GTP and forms a pseudosymmetric dimer with Ffh to coordinate SRP-receptor docking and release.

Sec61 Complex

The protein translocator (translocon) in the ER membrane featuring an hourglass-shaped central pore, a helical plug, and a hydrophobic lateral gate for the insertion of transmembrane segments into the phospholipid bilayer.

Sec61 Helical Plug

A short helical domain that seals the lumenal end of the Sec61 channel in the idle state and moves out of the pore upon ribosome docking and polypeptide insertion.

Sec61 Pore Ring

A ring of isoleucine residues situated at the constricted waist of the Sec61 translocon that forms a tight gasket around translocating polypeptides to prevent the leakage of small molecules.

Signal Peptidase

An ER lumenal enzyme that cleaves the N-terminal signal sequence from a nascent polypeptide during cotranslational or post-translational translocation.

Post-translational Translocation

The SRP- and SRP receptor-independent transport of completed polypeptides into the ER lumen through the Sec61 translocon, driven by Sec63 and BiP ATP hydrolysis.

BiP (Binding Immunoglobulin Protein)

An ATP-dependent Hsp70-family molecular chaperone in the ER lumen that ratchets translocating polypeptides through the translocon to prevent backsliding and assists in protein folding.

Sec63 Complex

An ER membrane protein complex that associates with the Sec61 translocon and stimulates BiP to hydrolyze ATP to ADP during post-translational translocation.

Topogenic Sequences

Hydrophobic peptide segments—including N-terminal signal sequences, internal stop-transfer anchor sequences, and internal signal-anchor sequences—that dictate the insertion and orientation of membrane proteins in the ER.

Stop-Transfer Anchor (STA) Sequence

A hydrophobic segment that halts translocation through the Sec61 translocon and exits laterally into the lipid bilayer, anchoring the protein with its N-terminus in the ER lumen and C-terminus in the cytosol.

Signal-Anchor (SA) Sequence

An internal hydrophobic segment of Type II and Type III proteins that serves as both the ER targeting sequence and the permanent membrane-spanning domain.

Type I Membrane Protein

A single-pass membrane protein containing a cleaved N-terminal signal sequence and an internal stop-transfer anchor, resulting in an exoplasmic/lumenal N-terminus and a cytosolic C-terminus.

Type II Membrane Protein

A single-pass membrane protein lacking a cleavable N-terminal signal sequence whose internal signal-anchor sequence has flanking positive charges on its N-terminal side, directing the N-terminus to the cytosol and the C-terminus to the ER lumen.

Type III Membrane Protein

A single-pass membrane protein with an internal signal-anchor sequence flanked by positive charges on its C-terminal side, directing the C-terminus to the cytosol and the N-terminus to the ER lumen.

Tail-Anchored Proteins

Integral membrane proteins that lack an N-terminal signal sequence and possess a hydrophobic transmembrane domain at the extreme C-terminus, which is inserted post-translationally by the Get pathway.

Get3

An ATPase that binds the hydrophobic C-terminal tail of tail-anchored proteins in the cytosol and docks with the dimeric Get1/Get2 receptor in the ER membrane.

Type IV Membrane Protein

A multipass transmembrane protein containing multiple membrane-spanning $\alpha$ helices, such as G protein-coupled receptors and the GLUT1 glucose transporter.

GPI Anchor

A glycolipid anchor composed of fatty acyl chains, inositol, glucosamine, mannose, and phosphoethanolamine that covalently anchors exoplasmic cell-surface proteins to the membrane.

GPI Transamidase

An ER lumenal enzyme that cleaves a precursor membrane protein near its stop-transfer anchor sequence and covalently attaches the new C-terminus to the amino group of a preformed GPI anchor.

Hydropathy Profile

A graphical plot measuring the total hydrophobicity of consecutive 20-amino-acid segments along a protein sequence, used to predict likely 22–25 residue transmembrane domains.

Dolichol Phosphate

A membrane-anchored polyisoprenoid lipid containing 75 to 95 carbon atoms that acts as the lipid carrier upon which the 14-residue N-linked oligosaccharide precursor is assembled.

Tunicamycin

An antibiotic that blocks the first step of N-linked glycosylation, preventing the transfer of N-acetylglucosamine-1-phosphate from UDP-GlcNAc to dolichol phosphate.

N-linked Oligosaccharide Precursor

A preformed 14-sugar core oligosaccharide, $(\text{Glc})_3(\text{Man})_9(\text{GlcNAc})_2$, synthesized on dolichol phosphate and transferred en bloc to an asparagine within an Asn-X-Ser/Thr tripeptide motif.

Calnexin and Calreticulin

ER chaperone lectins that selectively bind N-linked glycoproteins containing a single re-added terminal glucose residue ($\text{Glc}_1\text{Man}_9(\text{GlcNAc})_2$) to retain them in the ER for proper folding.

Dislocation (Retrotranslocation)

The transport of misfolded or unassembled ER lumenal proteins across the ER membrane into the cytosol for ubiquitinylation and degradation by the proteasome.

OS-9

An ER lumenal protein that recognizes mannose-trimmed oligosaccharides ($\text{Man}_{5-6}(\text{GlcNAc})_2$) on terminally misfolded glycoproteins, targeting them for dislocation to the cytosol.

Protein Disulfide Isomerase (PDI)

An ER lumenal enzyme containing a pair of catalytic cysteines that facilitates protein folding by forming, reducing, and isomerizing covalent disulfide bonds.

Ero1

An ER lumenal protein that oxidizes reduced protein disulfide isomerase (PDI) to regenerate active, disulfide-bonded PDI.

Unfolded Protein Response (UPR)

A signaling cascade activated by the accumulation of misfolded proteins in the rough ER that induces the transcription of genes encoding ER chaperones or triggers apoptosis if unmitigated.

Ire1

An ER transmembrane sensor that dimerizes and activates its cytosolic RNA endonuclease domain upon releasing bound BiP to accumulating unfolded proteins.

Hac1

A transcription factor whose unspliced precursor mRNA is cleaved in the cytosol by active Ire1; once spliced and translated, it enters the nucleus to activate the transcription of ER chaperone genes.