Secondary Structure, Tertiary, Protein Folding

Identify Helix Type

1. Find one hydrogen bond loop 2. Count number of residues (by number of Ca atoms in the loop) Here: 4 3. Count number of atoms in the loop (including first O and last H). Here: 13

The Beta Sheet

1. Strands of amino acids held together in sheets by inter-strand H-bonding 2. Bonding between backbone carbonyl oxygen and amide hydrogen on different strands. 3. strands of the Beta sheets tends to be twisted in a Beta barrel 4. The R-group lie perpendicular to the sheets; stick out on either face of the sheet. 5. Amino Acids such as isoleucine, valine, leucine prefer beta sheet/strand over alpha helix reduces steric hindrance

Protein Structure: Beta Sheet

1. The basic unit of a Beta sheet is called a Beta strand 2. Repeating unit 3. Beta sheets can form various higher level structures such as a Beta Barrel. (motif)

Define each amino acid in terms of its side chain

1. aliphatic 2. aromatic 3. basic 4. acidic 5. neutral

Characteristics of Beta Sheets

1. all hydrogen bond donors and acceptors are occupied in beta sheets 2. Antiparallel beta sheet is slightly more stable than parallel beta sheets 3. The hydrogen bonds in parallel beta sheets are not perfectly linear compared to hydrogen bonds in antiparallel beta sheet. 4. R groups alternate above and below the plane in beta sheets due to steric hindrance because the R groups are the most active residue. 5. more hydrophobic compared to alpha sheets

The Reverse Turn

1. turn "Reverse" turns: direction of polypeptide chains changes by ~180degrees 2. 70% are shorter than 7 residues in length 3. turns containing 2 residues are the most common (proline) 4. generally occur at the surface of the molecule 5. motif used to change the direction of the polypeptide chain

Domains in Common Proteins such as t-PA

5 different domains in Human Tissue Plasminogen activator: 1. serine-proteinase 2. kringle-1 3. kringle-2 4. EGF-like (epidermal growth factor) 5. fibrin-finger

Side Chain Interactions in Proteins

A. Hydrophobic interactions occur with the stacking of aromatic groups such as phenylalanine. B. Examples of hydrogen bonds in proteins

intrinsically disordered proteins

As many as a third of all human proteins may be unstructured or have significant content of unstructured segments. These intrinsically disordered proteins have properties that are distinct from classical structured proteins. Namely, they can lack a hydrophobic core, and instead may contain high densities of charged amino acid residues such as Lys, Arg and Glu. ( lysine, arginine, glutamate ) Pro residues are also prominent as they tend to disrupt ordered structures. The lack of an ordered structure can allow a protein to interact with multiple partners. The mammalian protein p53 plays a crucial role in the control of cell division. It features both structured and unstructured segments. An unstructured region at the carboxyl terminus interacts with at least four different binding partners (cyclin A, sirtuin, CBP bromo domain, s1008 (Beta Beta) and assumes a different structure in each of the complexes. structure is influenced by binding partner. fair amount of charge residues, lysine, arginine, glutamate, proline. disordered regions binds in diff. conformation depending on receptor. protein protein interaction can unstructured or disordered. no regular repeating partner.

Extended Chain vs. Beta Strand

Beta strand is not an extended polypeptide chain. It is twisted.

Which of the following is responsible for the maintenance of protein secondary structure? 1. Hydrophobic interactions 2. van der Waals forces 3. hydrogen bonds 4 disulfide cross-links 5. salt bridges

Hydrogen Bonds

Discuss the forces that maintain the tertiary structure of a protein.

Hydrophillic or charged R groups of amino acids of a globular protein interacts with water at its surface increasing the protein's solubility. Electrostatic interactions also maintain the tertiary structure of a protein between positively charged amino acids such as lysine (LYS) and the negatively charged amino acids such as aspartic acid. (ASP)

Outline the principles guiding folding of water soluble globular proteins.

Hydrophobic core is densely packed with hydrophobic R groups such as alanine, isoleucine, leucine, methionine, phenylalanine, tryptophan, tyrosine, valine. Hydrophilic or charged R groups are on the surface of the protein where they interact with water and increase the solubility of the protein. Positively charged amino acids with positively charged side chains are arginine (ARG), histidine (HIS), lysine (LYS). Negatively charged amino acids are aspartic acid (ASP) and glutamic acid(GLU).

Tertiary Structure

The total of all non covalent structure contained in a folded protein. Arrange and Folding pattern of secondary structural elements into a three-dimensional shape. Shape is more closely related to function than sequence.

What are the two types of beta sheet?

antiparallel and parallel

4. EGF-like (epidermal growth factor)

cloned, study structure and take the structure of individual domains and build it back into the molecule.

alpha helix

hydrogen bonding between carbonyl oxygen and the amide hydrogen of an amino acid in polypeptide 4 residues further down the chain