Lecture I-Structural Organization of Membrane Proteins.pdf

BIOC*4580 – Membrane Biochemistry Winter 2024 SECOND HALF Dr. Enoka Wijekoon [email protected] Office Hours: Mon & Wed: 2:00-3:00 PM Office: SSC 3517 Important Dates February 28: Quiz 2 March 15: Quiz 3 April 22: Final Examination – 8:30-10:30 AM Structural organization of membrane proteins Lectu...

BIOC*4580 – Membrane Biochemistry Winter 2024 SECOND HALF Dr. Enoka Wijekoon [email protected] Office Hours: Mon & Wed: 2:00-3:00 PM Office: SSC 3517 Important Dates February 28: Quiz 2 March 15: Quiz 3 April 22: Final Examination – 8:30-10:30 AM Structural organization of membrane proteins Lecture 1 Which amino acid is best described by the clue? Clue Replacement of the S atom of cysteine by an O atom would give this amino acid Smallest amino acid Isomer of leucine Forms disulfide bonds in the presence of O2 (dimerizes) R= -CH(OH)-CH3 Strongest absorbance of ultraviolet light Phenolic alcohol Best buffer at physiological pH Molecular formula C6H14N4O2 Thioether (sulfide) γ (gamma) carboxylic acid Answer Serine Glycine Isoleucine Cysteine Threonine Tryptophan Tyrosine Histidine Arginine Methionine Glutamate/Glutamic acid Functions of membrane proteins 1. Receptors – for extracellular signals (e.g. hormones) & membrane potential changes (most will span the membrane at least once) 2. Transporters – transport polar or charged molecules across the membrane (must span the membrane) 3. Enzymes – may span the membrane but most will be found on one side or the other of the membrane Membrane protein association with the membrane bilayer 1. Embedded in the membrane and removed only by using detergents or organic solvents that disrupts hydrophobic interactions: Integral membrane proteins Monotopic – interact with one leaflet Bitopic - spans the bilayer once Polytopic – span the membrane several times 2. Associate via hydrogen bonding or electrostatic attractions to PL head groups or hydrophilic parts of integral proteins and removed by changing pH or adding a chelator (removes stabilizing Ca2+): Peripheral membrane protein 3. Associate reversibly with the membrane: Amphitropic proteins Some things to think about… What are the different types of phospholipases? What are their specificities (see Lehninger 8ed p.352) Figure 10.14, Page 352 Soluble Proteins vs Membrane Proteins Soluble proteins are found in aqueous environments surrounded by water. They are folded in such a way to have hydrophilic amino acids in the exterior and hydrophobic amino acids in the interior The hydrophilic groups hydrogen bond with the surrounding water stabilizing the protein Hydrophobic R chains Myoglobin Hydrophilic R chains How do membrane proteins manage their H-bond groups? Polypeptide chains in membranes are surrounded by lipids and there are no water molecules present to form hydrogen bonds. The C=O and N-H groups of the peptide bonds and the side chains of several amino acids can act as hydrogen bond donors or acceptors The composition and the geometry of membrane proteins therefore must be carefully arranged to minimize the exposure of any unpaired hydrogen bonding groups to the surrounding hydrophobic milieu. Given serine and two ammonia molecules, hydrogen bonding exists between which pairs of atoms? A. B. C. D. (1,2)  (1,2) & (4,6) (1,2) & (4,5) (2,3) & (5,6) More things to review… What are hydrogen bonds? What types of groups can act as hydrogen bond donors and acceptors? This leads to Membrane proteins having a limited number of structural possibilities 1. A helix that crosses the whole membrane 2. Closed b –barrel with the connecting loops outside the membrane This buries all backbone hydrogen bonding groups in regular secondary structure elements that fully satisfy hydrogen bonding potential A short section of alpha-helical peptide is shown in the figure below. The O atom indicated by the heavy arrow (X) is hydrogen-bonded to the atom indicated by arrow… D A. B. C. D. A B C D A X H N H C R1 H O C N H C R2 O H C N H C R3 O H C N H B C R4 O H C N H C C R5 O C The  Helix  helix = simplest arrangement, maximum number of hydrogen bonds ▪ backbone winds around an imaginary longitudinal axis ▪ R groups extend out from the backbone ▪ 3.6 residues per each turn; ∼5.4 Å ▪ C=O of each amino acid H-bonds with NH of the amino acid 4 residues down from it (C=O of #1 with NH of # 5; C=O of #2 with NH of # 6 etc.,)