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The structural organization within proteins
Kevin SlepJune 13th, 2012
From Linear Peptide to a 3D Fold1951
Herman Branson Linus PaulingRobert Corey
The Amino AcidThe Building Blocks of Proteins
The 20 Amino AcidsThe Building Blocks of Proteins
The Peptide Chain, Primary StructureAssembled by the Ribosome During Translation
Peptide Backbone: Phi Psi AnglesLimits to their distribution
Ramachandran PlotEnergy limits to the Phi Psi Distribution
The Globular Protein FoldExterior: HydrophillicInterior: Hydrophobic
Soluble Proteins:
How would the organization of a Membrane Protein compare?
L
A
G
SV
E
T
R
K
D
I
P
N
Q
F
YM
H
CW
PackingCross Section of a Globular Protein
Interactions That Stabilize Protein Folds
Secondary StructureHelicesStrands
and Loops
First: How do we determine structure?
Our Tools:Solution NMR
Nuclear Magnetic Resonance
Distance ConstraintsDynamic Snapshot
X-ray Crystallography
Electron DensityStatic Snapshot
Secondary Structure: The -Helix
3.6 residues per turn
Secondary Structure: The -Helix
Helical Axis
Secondary Structure: The -HelixHelical Wheel – Hydropathy Plots
Helical Axis
Forms of Helices
Secondary Structure:The -Sheet: Parallel-Strands
Secondary Structure:The -Sheet: Parallel-Strands
Secondary Structure:The -Sheet: Anti-Parallel -Strands
Secondary Structure: LoopsLinkers, Variable Structrure, Active Site
Cystine: The Disulfide BondTwo Cysteines Covalently Bond (Oxidation)
Provides Added Stabilization to a Fold
Secondary Structure Prediction ToolsOnline Sites:
Predict Protein http://www.predictprotein.org/
Phyre http://www.sbg.bio.ic.ac.uk/phyre/
Jpred3 http://www.compbio.dundee.ac.uk/~www-jpred/
Secondary Structure:
Structure is Conferred by Main Chain Conformation and
Side Chain Conformation – PackingRotamers:
Favored Geometries/Energy States
Phenylalanine
How Secondary Structure is Organized:
Motifs and Tertiary Structure
Topology Diagrams
Jane Richardson (Duke Univ.)
Triose Phosphate Isomerase
Structural Motifs Hairpin
Structural MotifsHelix-Loop-Helix
Structural MotifsEF-Hand
Calmodulin: 4 EF Hands
Structural MotifsZinc_Finger
Two Histidines on a HelixTwo Cysteines on a Loop
Structural MotifsGreek Key
Structural MotifsGreek Key
Pre-albumin
Structural MotifsJelly Roll
Structural Motifs
Structural MotifsRossmann Fold
Nucleotide Binding
Helix-Turn-HelixDNA Binding Proteins
Four-Helix Bundle
Catalytic Triad
Aspartate, Histidine, Serine
TIM Barrel Domain
-Barrel
-Propeller Domain
Neuraminidase
Non-Protein Molecules That Play a Role in Structure and Function
The Heme Group in Hemoglobin
Cofactors
Non-Protein Molecules That Play a Role in Structure and Function
Water in PrealbuminFirst Hydration Shell
Ordered Water
Non-Protein Molecules That Play a Role in Structure and Function
Ions
Water in Prealbumin
How Do Proteins Fold?
Moving from a linear peptideTo a Motif
To a Domain
Protein Folding: Energy Landscape
Protein Folding: Pathways
Protein Folding: Help From Chaperones
Protein DomainsBuilt from Motifs
Domains solenoid – a curved structure
peridinin-chlorophyll-containing protein - trimer
Domains
WD40 protein
Domains
Helices and StrandsAlternate in the peptide
Domains
Saddle
and Domains
Helices and StrandsAre separated in the peptide
DNA ClampPCNA
Irregular Folds
Conotoxin, disulfide in yellow
Examples of Protein Structure
Structure Confers Function
Membrane ProteinsPorins
Membrane ProteinsAquaporins
Membrane ProteinsG-Protein Coupled Receptors
GPCR: Rhodopsin
Membrane ProteinsIon Channels
Potassium Channel
Viral ProteinsReovirus Core
Immunoglobulins
Signaling Molecules: G-protiens
Structural ProteinsClathrin
Structural ProteinsActin Filaments: Actinh
Structural ProteinsMicrotubules: Tubulin
Motor ProteinsKinesin
Motor ProteinsMyosin
Protein Folds – as of 200810562008
Various Folds Confer Dynamic Properties
T4 Lysozyme
Various Folds Confer Dynamic Properties
G-proteinsNucleotide-dependent Conformational change
Quaternary Structure
Oligomerization of the same protein, or multiple different proteins
Homodimer Heterodimer
Homotrimer Heterotrimer
Homotetramer Heterotetramer
The Coiled Coil
A common dimerizationmotif
Quaternary Structure
Quaternary Structure-globin E6V Mutation: Sickle Cell Anemia
Sickle Cell MalariaHeterozygotes are protected from malaria
PaulingHemoglobin is responsible
PyMol Demonstration
Discussion QuestionsOpen discussion on the PNAS paper by Pauling, Corey and Branson
What is the importance of tertiary structure for an active site?
Why is it important to study secondary and tertiary structure?
How important is it to know structure and what does structure tell us about function?
Can you predict the tertiary structure from primary or secondary structure.
Can you predict the quaternary structure from primary, secondary or tertiary Structure?
Why are some protein folds seen over and over again in nature – and used for different functions.
