Lecture 2 - Proteins Flashcards
How are amino acids classified?
- polar (uncharged)
- nonpolar
- basic (+)
- acidic (-)
Peptide bonds
- carboxyl carbon of one aa shares electrons w/ nitrogen of amino group from another aa
- loss of H2O (condensation rxn)
- strong, covalent bonds
What kind of interactions and/or noncovalent bonds help proteins fold?
- noncovalent: hydrogen bonds, electrostatic, van deer Waals
- hydrophobic clustering force
Common folding motifs of proteins
- α helix: N-H of a peptide bond is hydrogen bonded to CO 4 residues away
- β sheet: hydrogen bonding between different strands hold it together, aa in each strand project above and below the plane alternately
Why does a protein spontaneously refold after the denaturing agent is removed?
Because all the information needed for the 3D protein structure is found within the amino acid sequence
What are protein domains?
- modular units from which larger proteins are built from
- structural unit that folds mostly independently
How does a coiled-coil form?
When 2+ of the α helices have the hydrophobic region on one side of the strand –> wrap together and hydrophobic regions are on the inside of the coiled-coil
What is the SH2 domain?
A protein structure that responds to cell signals to cause selected proteins to bind to each other –> alter cell behavior
Domains of the Src protein
Src protein - functions in signaling pathways
- SH2 and SH3 domains: regulatory functions (respond to signals turning the kinase on/off)
- C terminal domain: gives kinase activity
idea = different domains have different functions
What do disulfide bonds do for a protein?
Example
Strengthens/reinforces the most favored conformation of the protein
acts as staples
Lysozymes retain their antibacterial activity for a long time due to disulfide bonds (cross-linkages)
What prevents insulin from being able to reform efficiently?
Interrupting their disulfide bonds because denaturation loses part of proinsulin
- proinsulin = assembly factor that has the info for insulin to reform spontaneously
What does the ability for a protein binding to a ligand with high affinity depend on?
The formation of a set of weak noncovalent bonds
- allows ligand + binding site to fit precisely together
How does a protein binding site form noncovalent bonds only with certain ligands?
the folding of a polypeptide chain creates crevices/cavities (binding site)
- contains set of aa that are specific for certain ligands (to form noncovalent bonds)
What are scaffold proteins?
Proteins w/ binding sites for multiple proteins or RNA molecules
What is the function of scaffold proteins?
Multiple binding sites = link together specific sets of interacting macromolecules and hold them in place
can also enhance the rate of reactions
Biomolecular condensates
Cellular structures built from proteins and often RNA that are held together by weak, changing interactions
Why are biomolecular condensates multivalent?
They have 1+ scaffold proteins that make multiple independent interactions w/ self or other macromolecules
Liquid-liquid phase separation
or liquid-liquid demixing
The process of biomolecular condensate formation
- fluctuating interactions (weak interactions are constantly forming and breaking) make it act like a liquid
Why is it important for domains to be low complexity and disordered to form a biomolecular condensate?
Because it mediates the weak reactions which ultimately form the condensate
