College 5

Thymine electron configuration..

α-helix Fig The  -helix. A. Polypeptide backbone showing the arrangements of the H-bonds. The N-H of the peptide bond make an H-bond with the C=O of a peptide bond 3+ a bit residues further along the chain. And this pattern repeats for every next peptide bond in the chain. B. Ribbon diagram with the polypeptide backbone drawn in. C. The ribbon symbolizing the  -helix.

Myoglobin Fig D Structure of Myoglobin, a small oxygen binding protein in muscle. Only the backbone of protein is indicated plus the hemegroup. The tube like structures represent  -helices. Myoglobin consists for 70% of  -helices. Helices are extremely popular in compact globular proteins because they allow the packing of an essentially very polar polypeptide chain into a protein with a very hydrophobic interior. The first protein for which a 3-D structure was obtained, myoglobin (Perutz and Kendrew , Nobel Prize Chemistry in 1962) showed 70% of a–helix (see figs 4.14 and 4.15).

Myoglobin Fig Fe(II) heme (ferroprotoporphyrin IX) shown liganded to a protein His and O 2 as it is in oxygenated myoglobin and oxygenated hemoglobin. Note that the heme is a conjugated system so that all of the Fe-N bonds are equivalent. Due to the presence of a second histidine close to the O 2 molecule, the O 2 must bind at an angle of about 45 o, thereby lowering the binding constant for O 2, but much more so for CO.

Membrane proteins: rhodopsin Fig Structure of Rhodopsin, the visual protein. Purple cylinders reflect  - helices, which span the membrane of a visual cell. The chromophore, retinal,is indicated in the center (light blue). Upon excitation the retinal chrompohore isomerizes around its C11-C12 double bond, which leads to a rearrangement of H-bonds in the protein structure, eventually leading to a small conformational change that eventually produces a signal to the brain.

Membrane proteins: photosynthetic reaction center Fig Structure of the bacterial photosynthetic reaction center. The transmembrane part consists of 11  -helices: 5 from the L-subunit (yellow), 5 from the M-subunit (red) and 1 from the H-subunit (green). The blue protein is a 4-heme cytochrome, linked to the reaction center, this cytochrome subunit is only there in some photosynthetic bacteria. The L and M-subunits are intrinsic membrane proteins, the H-subunit is mainly in the cytoplasm, the cytochrome is mainly in the periplasmic space. Upon excitation by a photon an electron is transferred by the bacteriochlorophyll cofactors from the periplasmic side of the protein to the cytosolic side.

Antiparallel and parallel β-sheet The energetically preferred dihdreal angles are (φ, ψ) = (–135°, 135°) (φ, ψ) about (–140°, 135°)(φ, ψ) about (–120°, 115°)

Anti-parallel β-sheet The second most-frequently occurring element of secondary structure is the antiparallel β-sheet. The N-H and C=O groups of a certain strand are hydrogen bonded to C=O and N-H groups of adjacent chains that run parallel to it, but in the opposite direction. The R-side groups in each strand alternately project above and below the plane of the sheet (see fig 4.20)

Anti-parallel β-sheet example: fibroin Fig 4.21 Silk fibroin is organized in an anti-parallel  -sheet.

Protein folding Proteins fold into a unique 3-D structure with a unique biological function. Even a mutation of one single amino acid may perturb this process in the sense that no longer a stable structure can be formed, or if it is formed it has no, or a much reduced, biological activity. Folded state → minimum in energy ‘Simple’ rules: 1.Two atoms can never be in the same place. Steric hindering is one of the major driving forces for the formation of secondary structure

Protein folding 2. Covalent connections between different parts of the chain can be made by di- sulfide bridges, involving two cysteines (see fig 4.25 and 4.26). A disulfide bridge in a protein is exceptionally stable. When a protein is being produced by the ribosome, a certain number of cysteine residues will be present.

Protein folding 3. Non-covalent interactions. As a result of ionic interactions, Van der Waals forces and hydrogen bonds, each type of protein has a particular three dimensional structure, which is determined by the order of the amino acids in the chain.

Folded proteins The final folded structure, or conformation, is the one in which the free energy is minimized (this minimum may not be unique for a system with so many degrees of freedom). For globular, water soluble proteins this is generally a compact conformation with a hydrophobic core and polar/charged residues (such as arginine, glutamine, histidine etc.) exposed to the aqueous phase Water → driving force

Folded proteins When polar residues are buried in the inside of a protein they are generally hydrogen-bonded to other polar amino acids or to the polypeptide backbone

Protein folding Fig 4.31 Free energy of a folding protein plotted as a function of the number of contacts between residues (not all are favourable) and the number of native contacts (meaning contacts that also occur in the functional protein). The potential energy drives the system to a conformation where a certain number of native contacts has been established, but the chain is not yet folded. Note that there are many possible pathways. Once this point is reached, the chain folds rapidly.

Denaturation Protein folding in a living cell is often assisted by special proteins called molecular chaperones. These proteins bind to partly folded polypeptide chains and help them progress along the energetically most favorable folding pathway. Chaperones are vital in the crowded conditions of the cytoplasm, since they prevent the temporarily exposed hydrophobic regions in newly synthesized proteins from associating with each other to form protein aggregates.

Structures

Denaturation Each protein normally folds up into a single stable configuration. However, this conformation often changes slightly when the protein interacts with other proteins in the cell. It is this modulation of the shape of proteins by its interaction with the ‘environment’ that is often crucial to the function of the protein.

Membranes All cells are enclosed in a plasma membrane. This container acts as a selective barrier that enables the cell to concentrate nutrients gathered from its environment and retain the products it has synthesized for its own use, while excreting waste products. Without its plasma membrane the cell could not maintain its integrity as a coordinated chemical system. Integral membrane proteins, like receptors and channels, cross the membrane. Receptors often have specific oligosaccharides attached to them that play a role in the recognition of specific compounds like hormones. Binding of a hormone then leads to a conformational change that is sensed at the cytosolic side of the membrane.

Transport through membranes A multitude of compounds must be transported into and out of the cell via the plasma membrane, into and out of the nucleus, mitchondria, chloroplasts, the golgi apparatus etc, including synthesized proteins!!!

Safety valves Structure of the mechanosensitive sensitive channel MscL. The channel opens in response to pressure and functions as a safety valve to protect the cell from lysis by osmotic pressure.

Cells & membranes Nucleus: Genome management Mitochondria & chloroplasts: Energy generation EP & Golgi complex: protein synthesis and modification

Ion pumps using ATP Fig 4.46 The ATP-driven K + -Na + exchanger. Na + and K + are exchanged and transported across the membrane against their gradients using ATP.