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#cellular membranes

2 public questions tagged with this topic.

Lipid Link Protein

Which of the following statements about lipid-linked proteins is true?

Lipid-linked proteins associate with membranes via covalent attachment of hydrophobic moieties rather than simple non-specific interactions. Several distinct modifications exist: N-myristoylation adds 14-carbon myristate to N-terminal glycine after methionine removal via amide linkage, palmitoylation S-acylates internal cysteine via thioester that is reversible, prenylation attaches 15-carbon farnesyl or 20-carbon geranylgeranyl to C-terminal cysteine in CAAX motif via thioether, and glycosylphosphatidylinositol anchor attaches to C-terminus via phosphoethanolamine bridging to glycan core terminated by phosphatidylinositol lipid inserting into outer leaflet. GPI anchoring provides stable extracellular membrane tethering for enzymes like alkaline phosphatase and adhesion molecules like CD59 complement regulator, conferring localization to lipid rafts and enabling regulated release via phospholipases. Contrary to notion of only extracellular occurrence without post-translational processing, lipidation occurs co- or post-translationally in cytoplasm, endoplasmic reticulum and Golgi and determines membrane targeting and signaling localization. Such detailed mechanistic insight is frequently examined in competitive tests including NEET, CUET, CSIR-NET and GATE where transporter classification, energetics and disease linkage are integrated into problem-solving questions.

Ref: Resh, Nat Chem Biol 2013, Lipid modifications; Fujita et al., J Lipid Res 2020, GPI anchors.

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Protein Sorting and Trafficking

The topology of membrane proteins is determined by:

Topological orientation of membrane proteins, defined by which loops face cytosolic versus exoplasmic or lumenal space, is encoded within polypeptide itself as a set of topogenic signals rather than imposed solely by external receptors. As nascent chain enters Sec61 translocon, hydrophobic segments can function either as start-transfer signal-anchor that opens lateral gate and initiates translocation of downstream region, or as stop-transfer sequence that halts translocation and partitions laterally into lipid bilayer through same gate formed by helices 2b and 7. Positive-inside rule, first documented in bacteria and conserved in eukaryotes, shows distribution of positively charged lysine and arginine residues flanking hydrophobic core strongly influences orientation because moving positive charge across membrane costs more energy and because Sec61 retains basic flanks cytosolically via acidic residues lining pore and anionic phospholipid attraction. Order of successive signal-anchor and stop-transfer elements determines multi-spanning topology polytopic proteins. SRP receptor presence or ATP hydrolysis modulates efficiency of targeting but does not rewrite inherent topological information encoded by charge bias and hydrophobicity profile of signal-anchor and stop-transfer sequences.

Ref: von Heijne G, Annu Rev Biophys 36: 2007, Membrane Protein Topology Determinants.

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