Polarity and The Membrane

The cell membrane is composed of two layers of phospholipids which have a polar phosphate head and non-polar tails. The layers are arranged so the inner portion of the membrane is comprised of non-polar fatty acid tails while the outer phosphate head is in contact with the aqueous extracellular fluid or cytosol.

Proteins spanning the inner portion of the phospholipid bilayer contain transmembrane domains which are non-polar. Which of the following amino acids WOULDN’T be found in the transmembrane domain of a protein?

Ion channels are proteins that span the membrane creating a pore between the intracellular fluid and the extracellular fluid. These channels allow the transport of charged and polar molecules to enter the cells as they are unable to cross the hydrophobic inner portion of the membrane. Which amino acids could be found on the fluid facing side of the ion channel?

I. Glutamine
II. Lysine
III. Phenylalanine

Proteins have a wide range of roles in the cells which include acting as catalysts that speed up chemical reactions (enzymes), binding antigens and activating different elements of the immune system (antibodies), and acting as cell surface receptors (e.g G-Protein Coupled Receptors) among others. In order to carry out these distinct roles, the proteins must assume the proper tertiary structure. Tertiary structure is driven by the hydrophobic effect which causes hydrophobic amino acids to fold and form the interior of proteins leaving hydrophilic residues exposed on the outer surface of proteins when in contact with a polar solvent such as water.

If this is true which amino acid is most likely to be found on the outer surface of an antibody in the blood?

Lipid rafts are specialized membrane nanodomains that act as signaling platforms involved in a number of physiological functions under normal and pathological conditions. These small (10–200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched domains compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein and protein-lipid interactions. The protein-lipid interactions typically occur when amino acid residues interact with the fatty acid tails of sphingolipids. Which amino acids can facilitate small raft stabilization via protein-lipid interactions?

Adpated From: Diaz Mario, Fabelo Noemi, Marin Raquel, Genotype-induced changes in biophysical properties of frontal cortex lipid raft from APP/PS1 transgenic mice (2012), Frontiers in Physiology, Vol. 3

Phosphopeptides are employed as probes in signaling transduction studies due to their ability to mimic cellular phosphoproteins. Phosphopeptides have been used to understand protein-protein and protein-ligand interactions due to their specificity as substrates to different binding domains in protein kinases, for example, the Src homology 2 (SH₂) domain in Src tyrosine kinase. The application of phosphopeptides has been challenging due to their restricted cellular uptake. Their limited uptake is due to the presence of negatively charged phosphate groups in their chemical structures, causing electrostatic repulsion with the negatively charged phosphate groups in the phospholipid bilayer. In order to allow for phosphopeptides to enter cells through the cell membrane, they need to contain positively charged residues and residues that allow them to interact with the inner portion of the cell membrane. What residue would allow it to interact with the inner portion of the membrane?

Adapted From: Shirazi, A.N.; Mozaffari, S.; Sherpa, R.T.; Tiwari, R.; Parang, K. Efficient Intracellular Delivery of Cell-Impermeable Cargo Molecules by Peptides Containing Tryptophan and Histidine. Molecules 2018, 23, 1536.

Amino acid chains of peptides can be displayed in a variety of different figures. The one below shows the relevant regions and the amino acids that make them up by using their one-letter abbreviations. Here the numbers represent the position of the amino acid within the peptide chain and by convention, the N-terminus of the peptide sequence is displayed on the left of the figure and labeled as residue 1. In this case, the letters below the sequence represent amino acid substitutions, and gaps in the amino acid chain help distinguish important regions of the peptide sequence.

Given this information how many nonpolar residues are found in the dimerization region?

Adapted From: A Model for Dimerization of the SOX Group E Transcription Factor Family Ramsook SN, Ni J, Shahangian S, Vakiloroayaei A, Khan N, et al. (2016) A Model for Dimerization of the SOX Group E Transcription Factor Family. PLOS ONE 11(8)

Amino acid chains of peptides can be displayed in a variety of different figures. The one below shows the relevant regions and the amino acids that make them up by using their one-letter abbreviations. Here the numbers represent the position of the amino acid within the peptide chain and by convention, the N-terminus of the peptide sequence is displayed on the left of the figure and labeled as residue 1. In this case, the letters below the sequence represent amino acid substitutions, and gaps in the amino acid chain help distinguish important regions of the peptide sequence.

Given this information, the substitution of the amino acid closest to the N-terminus in the dimerization sequence changes that position from:

Adapted From: A Model for Dimerization of the SOX Group E Transcription Factor Family Ramsook SN, Ni J, Shahangian S, Vakiloroayaei A, Khan N, et al. (2016) A Model for Dimerization of the SOX Group E Transcription Factor Family. PLOS ONE 11(8)