#membrane protein

Basics of Cell Biology

Which of the following proteins is an integral membrane protein?

Integral membrane proteins are defined by hydrophobic transmembrane segments, typically 20-25 residues forming alpha helix crossing hydrocarbon core stabilized by van der Waals and hydrogen bonding, or beta-barrel of multiple antiparallel strands as in VDAC. Extraction requires detergent disrupting bilayer rather than high salt. Aquaporin family represents classic multipass integral protein: tetramer in plasma membrane where each monomer with six transmembrane helices forms hourglass pore lined by NPA motifs Asn-Pro-Ala that orient water molecules in single file and aromatic-arginine constrict

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 10: Integral Membrane Proteins, Aquaporin.

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Plasma Membrane Proteins

Which protein functions as a water channel and facilitates rapid movement of water across membranes?

Water permeability of plasma membranes exceeds lipid diffusion requiring dedicated proteinaceous pores. Aquaporin family comprising thirteen human isoforms forms homotetramers in kidney proximal tubules, red cells, and brain astrocytes each monomer about twenty eight kilodaltons six transmembrane helices arrangement N-terminus cytosolic with two half-helices HB and HE entering membrane containing invariant NPA motifs meeting at center forming aqueous pathway hourglass shape. Extracellular vestibule leads to aromatic arginine constriction formed by Arg195 His180 Phe56 limiting diameter to two p

Ref: Agre et al., Aquaporin Water Channels – Structure and Function, Nobel Lecture 2003.

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Plasma Membrane Proteins

Which type of membrane protein is covalently linked to a lipid moiety, anchoring it to the membrane?

Lipid linkage expands repertoire of membrane association beyond hydrophobic transmembrane spans enabling reversible targeting. Four major classes documented: N-myristoylation fourteen-carbon saturated fatty acid amide linked to N-terminal glycine after methionine removal catalyzed by N-myristoyltransferase cotranslationally; S-palmitoylation sixteen-carbon palmitate thioester linked to cysteine catalyzed by DHHC palmitoyl acyltransferases reversible by thioesterases controlling trafficking; prenylation fifteen-carbon farnesyl or twenty-carbon geranylgeranyl thioether linked to C-terminal CAAX

Ref: Lodish et al., Molecular Cell Biology, 9th ed., Chapter 10, Lipid-Anchored Membrane Proteins.

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Plasma Membrane Proteins

Which of the following membrane proteins is involved in the 'Chloride-Shift' for CO₂ transport in RBCs?

Physiological transport of carbon dioxide from tissues to lungs uses chloride shift mechanism. CO2 diffusing into erythrocytes hydrated by zinc metalloenzyme carbonic anhydrase II to carbonic acid rapidly dissociating into bicarbonate and proton; proton buffered by deoxygenated hemoglobin promoting Bohr effect increasing oxygen release. Accumulating bicarbonate exported down gradient via anion exchanger Band 3 also termed AE1 SLC4A1 comprising fourteen transmembrane helices functioning as electroneutral one to one Cl- HCO3- antiporter exchanging extracellular chloride inward for intracellular

Ref: Alberts et al., Molecular Biology of the Cell, 6th ed., Chapter 11, Anion Exchanger Band 3 and CO2 Transport.

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Plasma Membrane Proteins

WB2:H25hich membrane protein type is only temporarily associated with the membrane and can be removed using high salt or

Operational definition of peripheral membrane proteins rests on extraction behavior under conditions preserving bilayer integrity. Integral proteins contain hydrophobic stretches of about twenty residues embedding deeply into acyl core requiring non-ionic detergent for solubilization. Peripheral proteins attach superficially through electrostatic attraction between clusters of lysine and arginine and acidic phospholipids phosphatidylserine phosphatidylinositol phosphate, via calcium bridging mediated by C2 domains, or via specific protein-protein interaction with cytoplasmic tails of integral

Ref: Lodish et al., Molecular Cell Biology, 9th ed., Chapter 10, Peripheral Membrane Proteins and Extraction.

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Lipid Link Protein

What type of lipid linkage does CD59 have?

CD59 protectin MIRL MAC-inhibitory protein exemplifies complement regulation through GPI anchoring. Gene located chromosome eleven encodes one hundred twenty eight amino acids including twenty six residue C-terminal GPI signal peptide removed in endoplasmic reticulum. Preassembled GPI precursor synthesized via stepwise addition of N-acetylglucosamine to phosphatidylinositol, deacetylation, addition of three mannose residues via PIG enzymes, and phosphoethanolamine addition is transferred en bloc by GPI transamidase containing PIG-K catalytic subunit forming amide bond between protein and phosp

Ref: Alberts et al., Molecular Biology of the Cell, 6th ed., Section: GPI-Anchored Proteins – CD59 and Complement Regulation.

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Membrane Transportation

The E1 conformation of Na+/K+ ATPase has:

Post-Albers scheme for P-type ATPases defines two principal conformers interconverting via phosphorylation. E1 state is outward closed, inward open, with N domain positioned to accept ATP and transmembrane domain exposing high affinity sodium sites to cytosol. Detailed structures from shark rectal gland enzyme show three sodium ions coordinated by oxygen atoms in pocket formed by M4, M5, M6 and M8 with micromolar affinity at cytosolic concentration about 10 millimolar, while potassium affinity submillimolar low because pocket incompatible with potassium dehydration geometry. Phosphorylation pr

Ref: Albers and Post Model, P-Type Pump Cycle, E1 High Na+ Affinity and E2 High K+ Affinity States.

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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 do

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

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