Chapter 3

PROTEINS
- molecule made from long chains of amino acids (50-2000)
- most of the cells dry mass; execute nearly all cell functions
- polypeptide backbone + sidechains
Shape and Structure of Proteins
Forces Affecting Cell Structure:
1.
van der Waals radius definite radius at which atoms may not overlap
2.
Noncovalent bonds usually form between sidechains
a. Hydrogen bonds
b. Electrostatic attraction
c. Van der Waals attraction
3.
Hydrophobic force in water, nonpolar side chains cluster inward
Proteins fold into a conformation of lowest energy
Conformation final folded structure of a protein due to the noncovalent interactions
Molecular chaperones may assist in protein folding; also a protein
Protein domains structural units of proteins that fold independently of each other (40350 amino acids)
Models of Protein:
1. Polypeptide backbone
2. Ribbon
3. Wire
4. Space-filling
-helix first protein folding pattern to be discovered; found in -keratin (skin, actin)
o Coiled-coil -helices wrapped around each other; particularly stable
-sheet found in fibroin (silk); found extensively in the core of many proteins
- parallel or antiparallel
Both result from H-bonds between N-H and C=O groups in polypeptide backbone
Proteins can be classified into families
Orthologs genes that are similar due to last common ancestor
Paralogs genes that are similar due to gene duplication
Some protein domains form parts of many different proteins
Domain shuffling joining of preexisting domains in new combinations
Protein modules subset of proteins that seem especially mobile during evolution
Larger protein molecules often contain more than one polypeptide chain
Binding site region on the proteins surface that interact with other molecules through
noncovalent bond
Protein subunits polypeptide chain in proteins that consist of several chains
(eg: Cro repressor protein; hemoglobin)
Many proteins have elongated fibrous shapes
Fibrous proteins
Intermediate filaments important part of the cytoskeleton
Extracellular matrix bind collections of cells to form tissues
Collagen 3 long polypeptide chains with glycine at every 3 rd position
Elastin large amount of unstructured polypeptide chains
Advantages of Protein Subunits:
1. Requires only a small amount of genetic information
2. Assembly and disassembly readily controlled
3. Errors in synthesis can be avoided
Subunits can form capsids
Many structures are capable of self-assembly; if not, assembly factors aid in formation
Ligand a substance bound by the protein; has a binding site
Binding Methods:

1. Surface-string
2. Helix-helix
3. Surface-surface
Antibodies aka immunoglobulins; bind to target molecule to deactivate or mark for
destruction
Equilibrium constant can be calculated from concentration of ligand, antibody, and
ligand-antibody complex
Enzymes are powerful and highly specific catalysts
Enzymes
- Determine the chemical transformations; act as catalysts
- Combine with substrates to form products
- Reduces activation energy by binding to transition states
- Can use simultaneous acid and base catalysis
Lysozyme catalyzes cutting of polysaccharide chains in cell walls of bacteria
Tightly-bound molecules add extra functions to proteins
Rhodopsin signal receptor protein made by photoreceptor cells in the retina
retinal changes shape upon exposure to light
Hemoglobin made up of 4 heme groups, each with a single iron atom binds reversibly
with O2
Carboxypeptidase cuts polypeptide chains; tightly-bound zinc ion forms transient bond
with substrate
Coenzymes small organic molecules that add extra function
Biotin found in enzymes that transfer a carboxylate group (COO -)
Vitamin substances that are not synthesized by the body and must be supplied in small
quantities
Molecular tunnels connect 2 or more active sites in a protein
Carbomoyl Phosphate Synthetase 3 active sites
Diffuse-limited reaction reactions efficient enough to be limited only by collision of particles
Multienzyme complex large protein assemblies that pass substrates from enzyme to enzyme
Cells regulate catalytic activities of its enzymes
Feedback inhibition product inhibits enzyme that acts earlier in the pathway
Allostery regulatory molecule that had different shape from substrate
- attaches to the regulatory site that communicates with active site; causes
conformational changes
Two ligands whose binding sites are coupled must reciprocally affect each others binding
Linkage wherein a proteins binding site undergoes conformational change induced by
another binding site
Positive linkage molecules prefer to bind to the same conformation
Negative linkage molecules prefer to bind to different conformations
Cooperative allosteric transition
Many changes in proteins are driven by protein phosphorylation
1. Phosphate group has 2 negative charges and can attract positively-charged amino
acid side chains
2. Phosphate group can for part of a structure that can be recognized by other protein
binding sites
Regulation of Cdk and Src protein kinases
A protein can act as a microchip

1. Cyclin-dependent protein kinase monitors balance of cyclin, and protein kinase

and phosphatase
a. Phosphate must be absent from one site
b. Phosphate must be present in another site
c. Cyclin must be present
2. Src protein
a. C-terminal phosphate must be removed
b. SH3 domain must be bound by a specific activating protein
Proteins that bind and hydrolyze GTP are ubiquitous in cellular regulation
GTP binds directly to protein instead of donating a phosphate group like ATP does
GTP-activating protein (GTPase) hydrolized to GDP
Ras monomeric GTPase; hydrolyzed to GDP and deactivates molecule
GTPase activating protein (GAP) binds to Ras to compel transformation of GTP to GDP
Guanine nucleotide exchange factor (GEF) binds to GDP-Ras to make it release GDP
Large protein movements can be generated from small ones
EF-Tu protein serve as elongation factor in protein synthesis
Switch helix crucial -helix; can start or shut down a reaction
Motor proteins generate forces possible for cell contraction, crawling, and swimming
ABC (ATP-binding cassette) tranporters pumps substrate into and out of bacteria
ATP synthase harness H+ gradient produced by ETC to produce the most ATP in the living
world
Protein machines an energetically favorable reaction that drives ordered series of
conformational changes
SCF ubiquitin ligase binds to target protein, adding multiubiquitin polypeptide
chains
scaffold protein: cullin; F-box protein
Induced proximity cells change location of protein by covalently modifying them