Protein Structure Flashcards
What in general can proteins do?
- Form the building blocks of the cells
- Enzymes promote chemical reactions
- Create channels at the membranes
- Act as chemical messengers, motors, hormones (e.g. insulin)
JUST A REMINDER:
- Protein molecules are made out of a chain of 20 possible amino acids
- They bind together via covalent peptide bonds => polypeptides
- Each type of protein has it’s unique amino acid sequence and shape
What is the general structure of a polypeptide chain?
- Polypetide backbone - repeating sequence of core atoms (-N-C-C-)
- End are chemically differentiated => directionality
- Amino group (NH3) = N-terminus
- Carboxyl group (COO-) = C-terminus - Side chains (NOT involved in forming peptide bonds) -> gives the unique properties
Look through a list of the common amino acids:
Peptide bonds keep the amino acids in order, while alowing free rotation -> how come the proteins stay in certain 3D shape then?
Thanks to noncovalent bonds - weak forces that when paired together can constrain the folding of the specific proteins
- e.g. electrostatic interactions, hydrogen bonds, van der Waals attractions, hydrophobic interactions
What would happen if we put a protein with a nonpolar side chain into a water?
Nonpolar side chains are hydrophobic (stay clear from polar water molecules, don’t want to make bonds with them) -> the chains would cluster together and “hide” from the water environment by folding inward = Hydrophobic interaction
How do we call the specific folded structure of a protein? What (in general terms) determines it?
Conformation funtions in a way that requires the least amount of energy
- folding process releases heat, is energetically favourable
How did we find out that the information needed for correct folding must be already contained in the amino acids?
In lab we may apply solvents which will get rid of the noncovalent bonds -> protein unfolds = DENATURED -> once solvent is removed, the original structure is reestablished = RENATURATION
Do all proteins always form correctly? Give a more specific example of a type.
Unfortunatelly no - some may misfold, form aggregates and damage cells and tissues e.g. Altzheimer’s, Huntington’s
- Specific exmple: prions - infectious misfolded proteins that may bind to normal proteins and disrupt their structure as well
- may spread within body as well as outside e.g. blood, contaminated food
Fill in: Although protein chains can fold into the correct conformation of their own…
they may call for assistence in the form of chaperone proteins
- e.g. may bind to partly folded chains and lead it via the most energetically favorable way
Look at different ways protein can be visualized (bacterial transport protein HPr):
- Backbone = overall organization of the polypeptide chain
- Wire model = adds the positions of the side chains
- Space-filled model = contour map of the protein surface
Can we find some common patterns of folding?
Yes. For instance single a helix (alpha) and B sheet (beta)
- formed by the hydrogen bonds between N- and C-terminus in the backbone
- the chain adopts regular, repeated pattern
How does the structure of alpha helix form?
Single polypeptide chain turns around itself (cylindrical style) -> hydrogen bond is made between every 4th amino acid, links C=O of one peptide bond to N-H of another => regular right-handed helix
- Shorter ones can be found embedded in the membrane as part of receptors or transport proteins
What is meant by coiled-coil? How do they form?
= term used for multiple alpha helices wraping around one another to form a stable structure
- forms when a helices have most of their nonpolar (hydrophobic) bonds on one side -> they fold them inward away from polar environment
How are beta sheets formed? Types? What do we associate them with?
Made when hydrogen bonds form between segments of polypeptide chains that lie side by side
-> same orientation = Parallel beta sheet
-> opposite orientation = Antiparallel beta sheet
=> form highly rigid structures, insoluable aggregates e.g. amyloid fibers
- in humans linked to Alztheimers, prion diseases
- in other (e.g. bacteria) could be beneficial
Describe the levels of Protein organization.
- Primary structure = amino acid sequance
- Secondary structure = specific folding e.g. a helices, B sheets
- Tertiary structure = full 3D polypeptide conformation
- Quaternary structure = multiple polypeptides in one
How else can we organize proteins?
- We may use protein domain as the organization unit = segment of the polypeptide chain that can fold indepepndently into stable structures (secondary structures)
- Different domains are associated with different functions
What do we mean by “instrinsically disordered sequences”?
Some proteins are so small they include only a single domain -> however with larger domain chains - they tend to be connected by unstructured polypeptide chains i.e. lack definite structure, can bend (apart from these the protein is still highly ordered)
Why could these unstructured segments be useful?
They enable flexibility in binding to all kinds of molecules, they can help scaffolding proteins bring together other proteins and make them interact, rubberlike fibers of elastin (allows recoiling after the skin was stretched)
How many combinations of a protein could exist (formula)? Do we have all of them in our body?
Protein sequences can be composed of 20 different amino acids -> 20n e.g. for a peptide of 4 amino acids it would be 20x20x20x20 = 160 000 possible combinations
We do NOT have all:
- we only use stable well-defined 3D conformations
- those that “behave well” e.g. don’t make unwanted aggregates
=> nonconforming were eliminated by natural selection
What is meant by Protein Families?
= categorization of groups in which its members share some common amino acid sequences
- BUT they mat perform slighty different functions (e.g. affecting different targets)
- E.g. serine proteases - enzymes in digestive system
Wha does the picture depict?
Structures formed by a combination of multiple protein subunits (each may contain more than one domain)
- any region on the protein’s surface that interacts with other molecules and forms noncovalent bonds with them = binding site
- complex of 2 symmetrical subunits = dimer (homodimers = identical, heterodimer = different)
Apart from alpha-helices and beta-sheets, larger structures can be formed. What are those?
- E.g. molecules arranged in a helix can keep extending indefinitely -> ultimetly forming filaments (like protein actin -> actin filaments)
- Others: tubes (microtubules), spherical shells (proteins for viral particles)
- NOTE: there are also structures build from a mixture of proteins and DNA/RNA e.g. ribosomes
What is the difference between globular and fibrous proteins?
Globular proteins take shape of a ball with irregular surface while fibrous proteins represent simple, elongated structures
