lesson five biochem= exam one

three-dimensional structure of proteins

are stabilized by non-covalent interactions and forces

protein segments can adopt regular secondary structures such as the alpha helix and the beta confirmation

tertiary structure= three dimensional fold adopted by a protein

quaternary structure= determiend by multi-subunit interactions

3d structure is determined by NMR, xray crystallography, and cryo-em

overview of protein structure

primary= covalent bonds linking amino acid residues in a polypeptide chain

secondary= recurring structural patterns

tertiary= 3D folding of polypeptide

quaternary= 2+ polypeptide subunits

primary structure

ribosomes use mRNA code to join the amino acids that make up proteins

this is the backbone of the protein, amino acid linkage

peptide bond

rigid and planar

3 covalent bonds seperate the alpha carbon of adjacent amino acid residue

resonance between carbonyl oxygen and the amide nitrogen

partial negative charge and partial positive charge sets up a small electric dipole, partial double bond character

cannot rotate freely

6 atoms of teh peptide group lie in a single plane

partial double bond character of C-N peptide

bond prevents rotation, limiting range of conformations

dihederal angles define peptide conformations

secondary structure

describes the spatial arrangement of the main-chain atoms in a segment of a polypeptide chain

• regular secondary structure= phi and psi remain the same throughout the segment

• common types= alpha helix, beta conformation, beta turns, random coils

largely stabilized by multiple weak noncovalent interactions

• hydrogen bonds

• hydrophobic interactions

• van der waals forces

• some disulfide bonds

alpha helix

simplest arrangement, maximum number of hydrogen bonds

common protein secondary structure

backbone wound around an imaginary longitudinal axis

R groups= protrude out from the backbone

each helix turn= 3.6 residues, 5.4 A

intrahelical hydrogen bonds

interactions between r groups can stabilize or destabilize the alpha helix

h bond formed between H atom attached to the electronegative N atom of residues n and the electronegative carbonyl oxygen of residue n+4

h bond formed between main chain atoms, -N-h***O=C-

the position and type of R group is important to the function of the protein and interacting partners (helical wheel)

structure:

• charged outside and hydrophobic (interact with others)

• middle= no side chains

proline disrupt the helix

introduces destabilizing kink in helix

nitrogen atom is part of rigid ring

rotation around N-c alpha is not possible

glycine

H atom is the R group

too much flexibility to stabilize the helix

handedness of helix

right handed= R groups protuding away from the helical backbone, most common

lefthanded= theoretically less stable, not observed in proteins

small electric dipoles= in each peptide bond align through hydrogen bonds

hand= direction of fingers

parameters of 310 helix

residue per turn= 3

rise= 0.2

atoms #= 10

phi= -49

psi= -26

parameters of alpha helix

residue= 3.6

rise= 0.15

atom #= 13

phi= -57

psi= -47

parameters of pi helix

residues/turn= 4.4

rise= 0.12

atom #= 16

phi= =57

psi= -70

beta conformation

b conformation= backbone extends into a zigzag, organizes polypeptide chains into sheets with the R group extending out of the plane of the sheet

b strand= single protein segment

b sheet= several strands in b conformation side by side

side view= always trans

beta sheets antiparallel

opposite orientation

occurs more frequently

more stable due to in-line H-bonding, making stronger

beta sheet parallel

same orientation

occur less frequently

less stable due to distorted H bonding

H bonds form between backbone atoms of adjacent segments, stabilize 2nd structure

angled in parallel strands, so overall bonding between parallel strands is weaker

beta turns

connect ends of two adjacent segments of an antiparallel beta sheet

• 180 turn

• involves 4 residues

• H bonds forms between 1st and 4th residue

type one beta turn

proline found residue two

bond between 1 and 4

type two beta turn

glycine found on residue three

bond between 1 and 4

occur in beta turns

gamma turns

involve three residues

180 turn

proline found on residue 2

ramachandran plot

top left= antiparallel beta sheets

right next to it= parallel beta sheet

long curled dots= right twisted beta sheets

final fourth label in that top left= collagen triple helix

bottom= right handed alpha helix

far right= left handed alpha helix

circular dichroism

common secondary structure can be assessed

measures differences in the molar absorption of left-handed vs. right-handed circularly polarized light

chromophore= peptide bond

look at slide to see the graph

amino acids that show alpha helix

Kristin Has Marvelous LACE Qtips

amino acids that show beta sheet

IVY For The Win

amino acids that show reverse turns

SPDNG

tertiary structure

overall three dimensional arrangment of all the atoms in a protein

weak interactions and covalent bonds hold interacting segments in position

quaternary structure

arrangement of 2+ separate polypeptide chains in a three dimensional complex

proteins= ethier be functional, enzyme hemoglobin or structural

four types of protein groups

1. fibrous proteins= arranged in long strands or sheets

2. globular proteins= folded into a spherical or globular shape

3. membrane proteins= embedded in hydrophobic lipid membranes

4. intrinsically disordered proteins= lacking stable tertiary structures

fibrous protein

gives strengths or flexibility to structures

simple repeating element of secondary structure

H2O insoluble due to high concentrations of hydrophobic residues

ex. alpha helix, beta conformation, collagen triple helix

alpha keratin

a keratin is a right-handed alpha helix

two strands of alpha keratin, oriented in parallel, wrap about each other to form a super-twisted coiled coil

super twisted coil= let handed

points of contact are rich in hydrophobic residues: ALA, VAL, LEU,ILE, MET, PHE

cross linked stabilized by disulfide bonds= common in cyestine

collagen

collagen found in connective tissue

2 structure= left handed alpha chains, repeating tripeptide unit GLY-X-Y, x is proline, y is 4-hyp

3 and 4 structure= right-handed twisting of 3 seperate polypeptides

cross-linked by covalent bonds involving Lys, HyLys, or His, cross link between secondary structures

links created by uncommon amino acid residues

scurvy

caused by lack of vitamin C

characterized by general degeneration of connective tissue

vitamin C is required for teh hydroxylation of proline and lysine in collagen

globular proteins

fold back on each other

more compact than fibrous proteins

enzymes, transport proteins, motor proteins, regulatory proteins, immunoglobin

each protein has a distinct structure, adapted for its biological function

example, myoglobin

• single subunit

• 8 alpha helical regions

• the hydrophobic effect

• binds heme

• O2 transport in muscle

intrinsically disordered proteins

lack definable structure

often lack a hydrophobic core

high density of charged residues (Lys, Arg, Glu, and Pro)

facilitates a protein to interact with multiple binding partners

intrinsically disorered segments can assume different structures

alpha/beta barrel

series of b-a-b loops arranged such that the b strands form a barrel

left handed

topology diagram

represent elements of secondary structure and the relationship among segments of secondary structure in a protein

protein family

siginficant similarity in primary structure and/or tertiary structure and function are in the same protein family

-4000 different protein families in the PDM

suprafamilies

2+ families that have little sequence similarity but the same major structure motif and have functional similarities