Protein Targeting to Organelles and Nuclear Transport

Vocabulary flashcards covering the mechanisms, protein complexes, targeting sequences, and regulatory factors involved in protein transport to the mitochondria, chloroplasts, peroxisomes, and nucleus.

Signal Sequence

A sorting signal composed of a unique amino acid sequence (typically a continuous stretch of $4-60$ amino acids) in a protein's primary sequence that is recognized by cellular proteins and acts as an address for delivery or retention.

Matrix-Targeting Sequence (MTS)

An N-terminal peptide sequence of $20-50$ amino acids forming an amphipathic alpha-helix with basic residues (Arg and Lys) on one side and hydrophobic residues on the other, directing proteins to the mitochondrial matrix.

TOM Complex

The translocon of the outer membrane of mitochondria; a protein complex containing receptor proteins (such as Tom20, Tom22, and Tom70) and a general import pore (Tom40) that transports precursor proteins across the outer mitochondrial membrane.

TIM Complex

The translocon of the inner membrane of mitochondria; channel complexes (such as Tim23/17 and Tim22/54) that translocate proteins across or insert them into the inner mitochondrial membrane.

Cytosolic Hsp70

A molecular chaperone that hydrolyzes ATP to maintain newly synthesized mitochondrial and chloroplast precursor proteins in an unfolded conformation suitable for translocation.

Matrix Hsp70

A mitochondrial chaperone anchored to the Tim44 protein that uses ATP hydrolysis to act as a molecular motor, pulling translocating proteins into the matrix and assisting in their folding.

Tim44

An inner mitochondrial membrane protein that anchors matrix Hsp70 to the Tim23/17 translocon to facilitate the import of precursor proteins into the matrix.

Stop-Transfer Anchor Sequence (Mitochondria)

A hydrophobic sequence found in inner membrane proteins (such as CoxVa) and intermembrane space proteins (such as cytochrome b2) that halts translocation through the Tim channel and causes lateral release into the inner membrane.

Oxa1

An inner mitochondrial membrane protein that recognizes internal hydrophobic sequences in imported proteins (such as ATP synthase subunit 9) or proteins translated in the matrix, inserting them into the inner mitochondrial membrane.

Tim9 and Tim10

Chaperone proteins in the mitochondrial intermembrane space that bind hydrophobic segments of multipass inner membrane proteins (such as the ADP/ATP antiporter) to guide them between the Tom40 pore and the Tim22/54 complex.

Erv1

An intermembrane space protein that cooperates with Mia40 to form two disulfide bonds in newly imported Tim9 and Tim10 proteins, trapping them in a folded state and preventing reverse translocation through Tom40.

Toc Complex

The translocon of the outer membrane of chloroplasts; a transport machinery that mediates the ATP-dependent post-translational import of unfolded precursor proteins across the chloroplast outer membrane.

Tic Complex

The translocon of the inner membrane of chloroplasts; a channel complex that works in concert with Toc to transport unfolded proteins across the chloroplast inner membrane into the stroma.

Twin-Arginine Translocation (Tat) Pathway

A chloroplast pathway driven by the thylakoid proton motive force in which fully folded proteins bearing an N-terminal twin-arginine signal are transported across the thylakoid membrane into the thylakoid lumen.

PTS1 (Peroxisomal-Targeting Sequence 1)

A conserved tripeptide sequence (Ser-Lys-Leu or SKL) located at the extreme C-terminus of most peroxisomal matrix proteins that is recognized by the cytosolic Pex5 receptor and is not cleaved upon import.

PTS2

An N-terminal peroxisomal targeting sequence present on a small subset of peroxisomal matrix proteins that is recognized by the cytosolic receptor Pex7.

Pex5

A cytosolic cycling receptor that binds C-terminal PTS1-bearing matrix proteins, forms a multimeric translocation complex with Pex14 in the peroxisome membrane, and is recycled to the cytosol by an ATP-dependent mechanism.

Pex14

A peroxisomal membrane docking receptor that associates with cargo-bound Pex5 to form a dynamic pore that adjusts to the size of folded matrix proteins during luminal import.

Pex1 and Pex6

Peroxisomal membrane-anchored AAA-ATPase proteins that use ATP hydrolysis to extract ubiquitinylated Pex5 from the membrane back into the cytosol for subsequent rounds of import.

Pex19

A cytosolic receptor and chaperone that binds membrane-targeting sequences of peroxisomal membrane proteins (such as PMP70) and delivers them to the Pex3/Pex16 complex on precursor membranes.

Pex3 and Pex16

A protein complex on ER-derived precursor membranes required for the proper insertion of peroxisomal membrane proteins to form peroxisomal ghosts.

Peroxisomal Ghost

An empty membrane vesicle formed by the insertion of peroxisomal membrane proteins into ER-derived precursor membranes, capable of importing folded matrix proteins to form a mature peroxisome.

Pex11

A protein required for the division and proliferation of preexisting mature peroxisomes.

Nuclear Pore Complex (NPC)

A massive transport complex spanning the inner and outer nuclear membranes, composed of multiple copies of approximately 30 different nucleoporins that regulates macromolecular traffic into and out of the nucleus.

Y-Complex

A structural assembly consisting of sixteen copies per nuclear pore complex (eight associated with each membrane) that forms the structural scaffold of the NPC.

FG-Nucleoporins

Nucleoporins that contain extended disordered segments composed of hydrophobic phenylalanine-glycine (Phe-Gly) repeats interspersed with hydrophilic regions, forming a gel-like sieve in the central channel of the NPC.

Nuclear Localization Signal (NLS)

An amino acid targeting sequence (commonly a short segment rich in basic Lys and Arg residues) that targets cytosolic proteins for import through the nuclear pore complex into the nucleus.

Nuclear Export Signal (NES)

A specific leucine-rich amino acid sequence that directs proteins from the nucleoplasm into the cytoplasm through nuclear pores.

Importin

A cytosolic nuclear transport receptor that recognizes NLS-bearing cargo proteins and mediates their translocation through the NPC via transient interactions with FG-repeats.

Exportin 1

A nuclear transport receptor that forms a cooperative export complex with an NES-containing cargo protein and Ran-GTP in the nucleoplasm to mediate export through the NPC.

Ran

A small monomeric G protein whose nucleotide-bound state (Ran-GTP vs. Ran-GDP) drives the directionality of macromolecular import and export across the nuclear envelope.

Ran-GEF (Guanine Nucleotide Exchange Factor)

A nuclear-localized enzyme that converts Ran-GDP to Ran-GTP by stimulating the exchange of GDP for GTP, establishing a high concentration of Ran-GTP in the nucleoplasm.

Ran-GAP (GTPase-Activating Protein)

A cytoplasmic enzyme associated with the cytoplasmic filaments of the NPC that stimulates Ran to hydrolyze GTP to GDP, triggering cargo release and maintaining high Ran-GDP levels in the cytoplasm.

NXF1/NXT1

A heterodimeric nuclear export receptor complex that binds processed mRNPs in the nucleoplasm and mediates their export through the NPC via a Ran-independent pathway.

Dbp5

An RNA helicase located on the cytoplasmic filaments of the NPC that uses ATP hydrolysis to disassemble NXF1 and NXT1 from exported mRNA during mRNP remodeling, preventing mRNA return to the nucleus.