Lecture 4: Three dimensional structure of Globular proteins Flashcards
the features of globular proteins the interactions that stabilize the structure of proteins
What are globular proteins?
- tertiary structure
- form vast majority of proteins
- structures determined experimentally (eg. x-ray crystallography)
- spherical (“globe-like”) proteins
- soluble
- form compact spheroidal molecules in water.
- All have tertiary structure and some have quaternary; in addition to secondary structure
What are globular proteins mostly responsible for?
- the work carried out by the cell
synthesis, metabolism, transport
What are general features of globular proteins?
lecture summary
- different regions of the polypeptide form sections of a-helix or B-sheet, joined by loops and irregular sections
- secondary structure form FRAMEWORK; rest of protein folds around them
- have distinct inside and outside (hydrophilic groups found outside, hydrophobic groups found inside)
- detailed structure largely determined by interactions involving side chains
- amino acids far apart in primary sequences can be brought together —> binding sites, active sites
What are the general features of globular proteins; from course book
- ) defined inside and outside; hydrophobic amino acid found inside, vice versa
- ) polypeptide chain folds into ONE OR MORE DOMAINS; framework of each domain consists of a combination of secondary structures ( a-helices & B-sheet)
- ) B-sheet usually twisted or wrapped into Barrel structure
- ) The polypeptide turns corners in a number of ways;
* includes B-turns,
* proline residues that cause a break in the a-helix
* bends and turns tend to occur on the surface - ) Some regions of globular protein cannot be classified in terms of secondary structure;
* regions can include extended loops, which allows change in direction of polypeptide chain
6.) The 3D structures of many proteins contain domains
What is a domain?
regions from the same polypeptide which are separately folded —> overall forming a compact region of tertiary structure
What are the interactions which stabilize the interactions that stabilize protein structure?
- ion pairs (salt bridges)
- hydrogen bonds
- disulfide bonds
- van der waals
- hydrophobic interactions
Describe ion pairs (salt bridges)
- electrostatic attraction between oppositely charged amino acid side chains
charge to charge interaction
- between (+) and (-) charged amino acid side chain
eg. Lys and Glu
What does the ion pair interaction depend on?
the pH
extremely low or high pH can break the salt bridges, thus denatures the protein
What are hydrogen bonds?
-ensure: protein forms secondary structure and folds up into the proper biologically active 3D shape
(many H-bonds in structure impose geometrical restraints directing proper folding)
- hydrogen is attached to an electronegative donor, donating a proton to an electronegative acceptor
- responsible for a-helix and B-sheet
- all polar groups can H-bond with water
- backbone bonding is a major determinant of secondary structure
- H bonding can also occur between the side chains of amino acids (eg. polar groups)
true or false, hydrogen bonding doesn’t really stabilize?
true
- little energy difference between folded and unfolded proteins as regards H-bonding
What are Van der Waals forces?
- very weak interactions between uncharged groups
- protein interior tightly packed- max contact
- occur between uncharged groups in the protein
- due to the large number of such interactions in a protein, MAKE A SIGNIFICANT CONTRIBUTION TO STABILITY
What are hydrophobic interactions ?
- interaction between non polar residues
- disrupts networks of H-bond (as it non polar residues cannot interact with water)
What is said to be the driving force of protein folding?
the need to remove hydrophobic side chains and cluster them together in the interior of the protein molecule
What are disulfide bonds?
- covalent cross links between 2 Cys residues
- do not cause folding —> but extra stability
- these are covalent bonds
- formed between pairs of Cysteine (Cys) amino acids (-SH-)
- only forms if cysteines become close together in the folded structure
- when such bonds form, this restricts the folding patterns available to polypeptide chains (this info can be used to determine complete covalent structure with knowledge of the primary structure)
DO NOT CAUSE PROTEIN FOLDING
true or false, hydrogen bonds, ionic bonds, hydrophobic interactions are weak non covalent bonds between side chains?
true
