Quiz 6 Flashcards
globular
soluble
fibrous
insoluble
primary level
sequence, covalent connection
secondary level
local structures, H bonds
tertiary level
overall 3D shape, all weak forces
quaternary level
subunit organization for multiple polypeptide chains
2,3,4 structures of proteins are formed and stabilized by
weak forces
how are the 2,3,4 structures of protein stabilized?
- hydrophobic bonds are formed wherever possible [directional]
- hydrophobic interactions drive protein folding [water entropy]
- ionic interactions are abundant on protein surfaces [opposite charges]
- van der Waals interactions are everything [best packing]
the tertiary structure or
fold of a protein
constraints in secondary structure
the planar character of the peptide group limits the conformational flexibility of the polypeptide chain
the alpha helix and the beta sheet allow
the polypeptide chain to adopt favorable phi and psi angles and to form hydrogen bonds
fibrous proteins
contain long stretches of regular secondary structure, such as the closed coils in a keratin and the stacked b sheets in b keratin
all peptide structure is based on the
amide plane
phi is the rotation angle around the
Ca-NH bond
psi is the rotation angle around the
Ca-CO bond
due to steric hinderance
some phi and psi angles are forbidden
G.N ramachandran
was the first to demonstrate the value of plotting phi, psi combinations from known protein structures
the entire path of the peptide backbone is know if
all phi and psi angles are specified
ramachandran plot
shows sterically allowed values for the angles phi and psi
conformation
changing shape without breaking a bond
configuration
requires breaking of a bond
secondary structures are the local backbone structures that are stabilized by
hydrogen bonds
- a helices
- b sheet
- b turns
the a helix
- stabilized by h bonds between backbone C=O and H-N groups
- because of amino acid chirality, the a helix has a right handed twist
H bonds between the amide carbonyl group of
Cai and the amide nitrogen [H] of Cai+4
pitch includes
3.6 residues[one turn], and at a 1.5A rise per amino acid residue, is equal to 5.4 A high
the a helix continued
- right handed twist
- residues per turn: 3.6
- rise per residue: 1.5A
- rise per turn, “pitch”: 3.6 x 1.5A = 5.4A
- h bonds between the amide carbonyl group and the amide nitrogen H
based on allowed phi-psi angles,
prolines angles are too restrictive
glycines angles are too permissive, flexible
B pleated sheets are composed of
B strands
antiparallel strands are connected by
a short turn
parallel strands are connected by
a longer loop
parallel b sheets are
less stable, bc they have imperfect H bond angles therefore >5 strands are requires
antiparallel b sheets
have straight short H bond, making them more stable. therefore <5 strands are required to form a sheet
the b turn or reverse turn
- allows the peptide chain to reverse reaction
- proline and glycine are prevalent in b turns
- carbonyl c of one residue is H bonded to the amide proton of a residue three residues away : C=O of a1 bonds with H-N of a4
fibrous proteins are usually
- insoluble[hair doesn’t dissolve in water]
they play a structural role in nature
3 types of fibrous proteins are discussed here
- a keratin
- b keratin
- collagen
a keratin
- a fibrous protein found in hair, fingernails, claws, horns and beaks.
- heptad repeat[7]: (a-b-c-d-e-f-g)n , where a and d are non polar, and b, c, e, f, and g are polar amino acid residues
- this primary structure promotes association of a helices to form coiled coils
the coiled coil is a
bundle of a helices wound into a superhelix
the left handed twist of the superhelix
reduces the number of resides per turn to 3.5 so that the positions of the side chains repeat every 7 residues called a heptad repeat of hydrophobic residues
b keratin
fibrous protein that forms extensive b sheets
b keratin are found in
silk fibers and bird feathers
b keratin have
- alternating sequence of two residues [GLY-ALA OR SER)n
- since side chains of a b sheet extend alternately above and below the plane of the sheet, this places all glycine on one side and all alanine or serines on the other side
stacking sheets give silk strength due to close packing van der Waals, this allows
glycine on one sheet to stack with glycine on an adjacent sheet, and on the other side ALA/SER residues mesh knobs into holes with another sheet
collagen helix
the principal component of connective tissue(tendons, cartilage, bones, teeth)
- three intertwined polypeptide chains
the collagen triple helix, 2 structure
- long stretches of the 3 among-acid repeat [GLY- PRO-PRO/HyP)n
- the unusual amino acid composition of collagen is unsuited for right handed a helices or b sheets
- much more extended than a helix with a rise per residue of 2.9A, 3.3 residues per turn
collagen triple helix
- unusual left handed helices wrap with a right handed superhelical twist
Poly(Gly-Pro-Pro) a collagen like
right handed superhelix composed of three left handed helical chains
in a collagen triple helix, every third residue faces the center of the helix
only glycine fits here
glycine, proline and HyP suit
the constraints of phi and psi
a keratin (hair and claw)
coiled coil has a “heptad repeat” 7 amino acid residues (a, b, c, d, e, f, g)n, where a and d are non polar and pack knobs into holes
b keratin (silk and feather)
stacked B sheets structure has an alternating repeat (Gly/Ala/Ser)n, where glycine sides pack extremely close together and Ala/Ser sides pack together, knobs into holes
collagen triple helix (bone, teeth)
has a (Gly-Pro-HyPro)n repeat that forms an elongated left handed helical structure that tightly intertwines three strands in a right handed super helix with glys packed inside
non polar residues tend to occur in
the protein interior and polar residues on the exterior
a proteins tertiary structure consist of secondary structural elements that combine to form
motifs and domain
throughout evolution,
a proteins structure Is more highly conserved than its sequence
globular proteins
are more numerous than fibrous proteins, and are more spherical
globular proteins functional diversity comes from
- the large number of folded structures that polypeptides adopt
- the varied chemistry of the side chains of the 20 amino acids
tertiary structure of globular proteins [PRINCIPLES]
- helices abd sheets make up the core
- most polar residues face the outside of the protein and interact with the solvent
- most hydrophobic residues face the interior of the protein
- van der Waals packing of residues is close
- the empty space in the form of small cavities allow for motion
principles learned from looking at atomic structures solved by NMR and X-ray crystallography
- large number H bonds
- helices and sheets often pack close together
- peptide segments between secondary structures tend to be short and direct
- proteins fold to form most stable structures
stability arises mainly from
- formation of large numbers of intramolecular h bonds
- reduction in the surface area accessible to solvent: COMPACT STRUCTURE
why do a helices and beta sheets form the core
- protein core is hydrophobic
- polar N-H and C=O groups of the peptide backbone must be neutralized in the hydrophobic core
the extensively h bonded nature of a helices and b sheets is ideal for
neutralizing the backbone amides in the hydrophobic core of globular proteins
the helices and sheets in the core of a globular protein family
are typically constant and conserved in sequence and structure
the protein surface is different in many ways
- protein surface composed of short loops and tight turns.loop/turn sequences are more variable in protein families
- the surface is a complex and irregular landscape of different structural elements
- interactions are the basis for enzyme-substrate binding, cell signaling, and immune responses and all other protein functions
segments that are not helices or sheets are referred to as
random coil
- most of these segments are neither coiled nor random
structure of random coil segments are stabilized by side-chain
tertiary interactions with the rest of the protein
a helices on a protein surface are usually
- amphiphilic, with polar and charged residues facing the solvent and non polar residues facing the interior
some a helices are
hydrophobic and buried in the protein interior
some helices are
polar and entirely solvent exposed
domains
compact, folded protein structures that are usually stable by themselves in aqueous solution
multidomain proteins typically are the
sum of the functional properties and behaviors of their constituent domains
motifs
are small folding topologies found in a diversity of proteins
the need to bury hydrophobic residues inside the protein leads to
formation of layers of structure in the protein
more than half the known globular proteins have
two layers of backbone, with one hydrophobic core [this is the minimum for folded domains]
these intrinsically disordered proteins
do not possess uniform structural properties but are still essential for cellular function
these proteins are characterized by a nearly complete
lack of structure, with high flexibility adopt well defined structures in complexes with their target proteins are characterized by an abundance of polar residues and a lack of hydrophobic residues
proteins with quaternary structure contain
- multiple subunits [each its own polypeptide chain]
subunits are usually arranged symmetrically
- open and closed
what are the forces quaternary association?
- typical Kd for two subunits: 10^-8, 10^-16, tight binding
- entropy loss due to association of subunits is unfavorable [negative entropy]
- entropy gain for water molecules due to burial hydrophobic groups is very favorable [positive entropy]
open symmetry
the structure of a typical microtubule, showing the arrangement of the a and b monomers of the tubular dimer
advantages of quaternary structure
- stability
- genetic economy
- assembly of catalytic sites between subunits
- cooperativity
protein stability depends primarily on
hydrophobic effects and secondarily on electrostatic interactions and h bonds
protein structure and function
- structure depends on sequence and on weak non covalent forces
- the number of protein folding patterns is large but finite
- structures of globular proteins are marginally stable (G= -5 to -10 kj)
- marginal stability facilitates motion
- motion enables function
the cellular environment imposes constraints on
the weak forces that preserve protein structure and function
denaturation
loss of structure and function
proteins can be denatured by
heat or cold in some cases
- high conc of chaotropic agents, guanidinium HCl and urea
a folding protein follows a
pathway from high energy and high entropy to low energy and low entropy thus these state functions are at odds keeping delta G of folding small
molecular chaperones assist
protein folding via an ATP dependent mechanism
amyloid diseases result from
protein misfoldingg
what factors play a role in protein folding processes?
- secondary structures
- hydrophobic collapse
- long-range interactions
- molten globule
- van der Waals packing
why are chaperones needed if the information for folding is inherent in the sequence?
- to protect from diseases caused by protein misfolding
- to protect newly formed proteins
