Protein Structure Protein Structure BasicsBasics
Presented byPresented by
Alison Fraser, Christine Lee, Alison Fraser, Christine Lee, Pradhuman Jhala, Corban Pradhuman Jhala, Corban
RiveraRivera
Importance of ProteinsImportance of Proteins
Muscle structure depends on Muscle structure depends on protein-protein interactionsprotein-protein interactions
Transport across membranes Transport across membranes involves protein-solute interactionsinvolves protein-solute interactions
Nerve activity requires transmitter Nerve activity requires transmitter substance-protein interactionssubstance-protein interactions
Immune protection requires Immune protection requires antibody-antigen interactionsantibody-antigen interactions
OverviewOverview
Primary StructurePrimary Structure Secondary StructureSecondary Structure Tertiary StructureTertiary Structure Quaternary StructureQuaternary Structure
Primary StructurePrimary Structure Polypeptide chains Polypeptide chains
Amino AcidsAmino Acids Largest polypeptide Largest polypeptide
chain approx has chain approx has 5000AA but most have 5000AA but most have less than 2000AAless than 2000AA
Amino Acid Basic Amino Acid Basic Structure HStructure H22N-CH-N-CH-COOHCOOH
Arrangement of the 20 Arrangement of the 20 amino acids in the amino acids in the polypeptide is the amino polypeptide is the amino acid sequence which acid sequence which composes the primary composes the primary structure of the proteinstructure of the protein
National Genome Research Institutegenome.gov
http://www.people.virginia.edu/~rjh9u/aminacid.html
20 Amino Acids
Nonpolar,hydrophobic
Polar, uncharged
Polar, charged
Amino Acid ClassificationAmino Acid Classification
A Venn diagram showing the relationship of the 20 naturally occurring amino acids to a selection of physio-chemical properties thought to be important in the determination of protein structure.
StereochemistryStereochemistry
Configuration of amino acids in proteinsConfiguration of amino acids in proteins The CORN LawThe CORN Law
Bond FormationBond Formation
Linking two amino Linking two amino acids togetheracids together
Definitions (N-Definitions (N-terminal, C-terminal, terminal, C-terminal, polypeptide polypeptide backbone, amino backbone, amino acid residue, side acid residue, side chains)chains)
http://web.mit.edu/esgbio/www/lm/proteins/peptidebond.html
Primary StructurePrimary Structure
What is a native protein?What is a native protein? Protein conformation & problem of Protein conformation & problem of
protein foldingprotein folding Hydrophobic, hydrophilicHydrophobic, hydrophilic ChargeCharge ChaperonesChaperones
Special Purpose Amino Special Purpose Amino AcidsAcids
ProlineProline
CysteineCysteine
IntroductionIntroduction Peptide bond geometryPeptide bond geometry Ramachandran plotRamachandran plot StructuresStructures
Protein Secondary Protein Secondary StructureStructure
Regular local structures formed by Regular local structures formed by single strands of peptide chain due single strands of peptide chain due to constraints on backbone to constraints on backbone conformationconformation
Peptide BondPeptide Bond
http://cmgm.stanford.edu/biochem/biochem201/Slides/
Peptide Bond Peptide Bond
Resonance Resonance C-N bond length of the peptide is C-N bond length of the peptide is
10% shorter than that found in usual 10% shorter than that found in usual C-N amine bondsC-N amine bonds
Peptide bond planer Peptide bond planer ωω, angle around peptide bond, , angle around peptide bond,
0000 for cis, 180 for cis, 18000 for trans for trans
Ramachandran PlotRamachandran Plot
http://hykim.chungbuk.ac.kr/lectures/biochem/4-5/fig6-9(L).jpg
Alpha HelixAlpha Helix
http://cmgm.stanford.edu/biochem/biochem201/Slides/
Alpha HelixAlpha Helix
Left-handedLeft-handed Right-handedRight-handed
http://www.rtc.riken.go.jp
Alpha Structure FeaturesAlpha Structure Features
3.6 residues per turn3.6 residues per turn 5.4 angstroms in length per turn5.4 angstroms in length per turn carboxyl group of residue i hydrogen carboxyl group of residue i hydrogen
bonds to amino group of residue i+4bonds to amino group of residue i+4
Helix StructuresHelix Structures Φ ψ H Bond R/t Φ ψ H Bond R/t
A/tA/tAlpha Alpha -57.8 -47 i, i + 4 3.6 -57.8 -47 i, i + 4 3.6 1313
3-10 Helix -49 -26 i, i + 3 3.0 3-10 Helix -49 -26 i, i + 3 3.0 10 10
Pi Helix Pi Helix -57 -80 i , i + -57 -80 i , i + 5 4.4 165 4.4 16
http://broccoli.mfn.ki.se
More Helix StructuresMore Helix Structures
TypeType ΦΦ ψψ commentscomments
CollagenCollagen -51-51 153153 Fibrous proteinsFibrous proteinsThree left Three left
handed helicieshanded helicies(GlyXY)n, X Y = Pro / (GlyXY)n, X Y = Pro /
LysLys
Type II helicesType II helices -79-79 150150 left-handed helicies left-handed helicies formed formed by by polyglycinepolyglycine
Beta Sheet Beta Sheet
http://www.rothamsted.bbsrc.ac.uk/notebook/courses/guide/images/sheet.gif
Beta Sheet FeaturesBeta Sheet Features
Sheets can be made up of any Sheets can be made up of any number of strandsnumber of strands
Orientation and hydrogen bonding Orientation and hydrogen bonding pattern of strands gives rise to flat pattern of strands gives rise to flat or twisted sheetsor twisted sheets
Parallel sheets buried inside, while Parallel sheets buried inside, while Antiparallel sheets occurs on the Antiparallel sheets occurs on the surfacesurface
More Beta StructuresMore Beta Structures
Beta Bulge chymotrypsin (1CHG.PDB) involving residues 33 and 41-42
Anti parallel
Beta Twist pancreatic trypsin inhibitor (5PTI)0 to 30 degrees per residue
Distortion of tetrahedral N atom
http://broccoli.mfn.ki.se
Beta turnsBeta turns
i + 1 Pro
i + 2 Pro or Gly
i + 3 Gly
http://rayl0.bio.uci.edu/~mjhsieh/sstour/image/betaturn.png
Interactions Interactions
Covalent bondsCovalent bonds Disulphide bond (2.2 Disulphide bond (2.2 00A) between two Cys A) between two Cys
residuesresidues
Non-covalent bondsNon-covalent bondsLong range electrostatic interactionLong range electrostatic interaction
Short range (4 Short range (4 00A) van der Waals interactionA) van der Waals interaction
Hydrogen bond (3 Hydrogen bond (3 00A)A)
Tertiary Protein Tertiary Protein StructureStructure
Defines the three dimensional Defines the three dimensional conformation of an entire peptide conformation of an entire peptide chain in spacechain in space
Determined by the primary structureDetermined by the primary structure Modular in natureModular in nature
Aspects which determine Aspects which determine tertiary structuretertiary structure
Covalent disulfide bonds from Covalent disulfide bonds from between closely aligned cysteine between closely aligned cysteine residues form the unique Amino Acid residues form the unique Amino Acid cystine.cystine.
Nearly all of the polar, hydrophilic R Nearly all of the polar, hydrophilic R groups are located in the surface, groups are located in the surface, where they may interact with waterwhere they may interact with water
The nonpolar, hydropobic R groups The nonpolar, hydropobic R groups are usually located inside the are usually located inside the moleculemolecule
Motifs and DomainsMotifs and Domains
Motif – a small structural domain Motif – a small structural domain that can be recognized in a variety that can be recognized in a variety of proteinsof proteins
Domain – Portion of a protein that Domain – Portion of a protein that has a tertiary structure of its own. has a tertiary structure of its own. In larger proteins each domain is In larger proteins each domain is connected to other domains by short connected to other domains by short flexible regions of polypeptide. flexible regions of polypeptide.
Modular Nature of Modular Nature of ProtiensProtiens
Epidermal Growth Epidermal Growth Factor (EGF) Factor (EGF) domain is a module domain is a module present in several present in several different proteins different proteins illustrated here in illustrated here in orange.orange.
Each color Each color represents a represents a different domaindifferent domain
Domain ShufflingDomain Shuffling
Occurs in evolutionOccurs in evolution New proteins arise by joining of New proteins arise by joining of
preexisting protein domain or preexisting protein domain or modules.modules.
Quaternary StructureQuaternary Structure Not all proteins have Not all proteins have
a quaternary a quaternary structurestructure
A composite of A composite of multiple poly-peptide multiple poly-peptide chains is called an chains is called an oligomer or oligomer or multimericmultimeric
Hemoglobin is an Hemoglobin is an example of a tetramerexample of a tetramer
Globular vs. FibrousGlobular vs. Fibrous
Protein FoldingProtein Folding
Protein folding constitutes the Protein folding constitutes the process by which a poly-peptide process by which a poly-peptide chain reduces its free energy by chain reduces its free energy by taking a secondary, tertiary, and taking a secondary, tertiary, and possibly a quaternary structurepossibly a quaternary structure
ThermodynamicsThermodynamics Proteins follow Proteins follow
spontaneous spontaneous reactions to reach reactions to reach the conformation the conformation of lowest free of lowest free energyenergy
Reaction Reaction spontaneity is spontaneity is modeled by the modeled by the equation equation ΔΔG= G= ΔΔH-H-TTΔΔS S
Molecular VisualizationMolecular Visualization Goal: Clear Goal: Clear
visualization of visualization of molecular structuremolecular structure
Different visualization Different visualization modes elucidate modes elucidate different molecular different molecular propertiesproperties
Some representations Some representations include Ribbons, include Ribbons, SpaceFill and SpaceFill and BackboneBackbone