Transcript Protein Structure - Chemistry Courses: About: Department

Protein Structure
C483 Spring 2013
1. Which statement is false about a globular protein that performs its biological
function as a single independent polypeptide chain?
A) Its tertiary structure is likely stabilized by the interactions of amino acid side chains
in non-neighboring regions of the polypeptide chain.
B) It could contain α-helices that are stabilized by hydrogen bonding.
C) It likely has extensive quaternary structure to maintain its globular shape.
D) Non-covalent forces are the primary source of stability for the secondary and
tertiary structure.
2. The conformation of the backbone of a polypeptide is described completely by the
angle(s) of rotation about which bond(s)?
A) The peptide bond only.
B) N-Cα only.
C) N-Cα, Cα-C and C-N bonds.
D) N-Cα and Cα-C bonds only.
3. Which structure indicates the proper
hydrogen-bonding pattern between amino
acids in an α-helix? (Dashed lines represent
the hydrogen bonds.)
4. What would you expect about the formation of an α-helix for a segment of
a protein chain that contains lysine approximately every fourth residue with
all other residues being mostly hydrophobic?
A) Helix formation would be favored at low pH.
B) Helix formation would be favored at high pH.
C) Helix formation would be favored at neutral pH.
D) Helix formation would never occur regardless of pH.
5. Supersecondary structures that contain recognizable combinations of αhelices, β-strands and loops (e.g. the Greek Key) are called ________.
A) domains
B) folds
C) homologous regions
D) motifs
6. The principle forces holding subunits of an oligomeric protein to each other
are ________.
A) peptide bonds
B) hydrophobic interactions
C) covalent bonds
D) disulfide bonds
Protein Structure
• Configuration and
conformation
• Native structure
– Fibrous
– Globular
• Atomic level and
cartoon level
Structural Determination
• Crystallography
• NMR
Structural Hierarchy
C483 goals
• Secondary structure dictated by
– Peptide bond structure
– Atomic level intermolecular interactions
• Tertiary and quaternary structure
– Importance to protein folding and activity
– Familiar with vocabulary so that you can read a
paper to learn the details
Peptide Bond
• Resonance
– 6 planar atoms
form a unit
• Highly polar
• Trans vs cis
conformation
Conformational Flexibility
• If each peptide
bond is relatively
locked, backbone
conformation can
be defined by phi
and psi
• NOT cis/trans
– Both stuctures to
the right are
trans
Ramachandran Plots
Alpha Helix
• Right handed
• Polarity
• Phi = -57o and
psi = -47o
• n and n + 4
• Ala vs. Tyr
• Gly and Pro
• The average ahelix is 12
residues long.
What is its
length in nm?
• How many
amino
acids/turn of
an alpha helix?
Amphipathic Helices
Structural Implications
Coiled-Coil
Placement in Protein
Beta-Sheets
Real Beta Sheets
• Technically, often
tertiary structure
• Generally
bent/twisted
• Alternating
sidechains can
lead to
amphipathic
sheets
Loops and Turns
• Nonrepeating
• Change of
direction
• Turns have about
4 residues
• Internal H-bonds
• Gly, Pro
Tertiary Structure
• Longer range
interactions of
secondary
features
• Driven by
hydrophobic
effect
• Disulfide
bridges
• Diversity
Tertiary Structure
• Too many shapes to memorize
• But not an infinite number of possibilities
• Take away the ability to read a paper
– Discussions of motifs and why important
– Discussion of domains and why important
Motifs
(Super Secondary Structure)
• Recognizable
combinations
of helices,
loops, and
sheets
• Match
– Helix-loophelix
– Helix bundle
– Hairpin
– b-sandwich
Studying Motifs
• Some Motifs are
highly studied
• Know the Lingo
– Leucine zipper
– Zinc finger
• Often have
recurring
applications
Domains
• Discrete,
independently folded
unit (may maintain
shape when cleaved
on loop)
• May have separate
activities: “ATP
binding domain” or
“catalytic domain”
• Similar activity =
similar structure
across many proteins
• Binding pockets at
interfaces
How many
domains?
Common Domains
Quaternary Structure
• Multiple
subunits:
Oligomers
• Homodimer,
heterotrimer
• Advantages
– Economy
– Stability
– regulation
a2
a3
a2b2
From your discussion paper…
Answers
1.
2.
3.
4.
5.
6.
C
D
B
B
D
B