Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... ·...
Transcript of Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... ·...
![Page 1: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/1.jpg)
Protein Structure Protein Structure BasicsBasics
Presented byPresented by
Alison Fraser, Christine Lee, Alison Fraser, Christine Lee, PradhumanPradhuman JhalaJhala, , CorbanCorban RiveraRivera
![Page 2: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/2.jpg)
Importance of ProteinsImportance of Proteins
Muscle structure depends on proteinMuscle structure depends on protein--protein protein interactionsinteractionsTransport across membranes involves proteinTransport across membranes involves protein--solute interactionssolute interactionsNerve activity requires transmitter substanceNerve activity requires transmitter substance--protein interactionsprotein interactionsImmune protection requires antibodyImmune protection requires antibody--antigen antigen interactionsinteractions
![Page 3: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/3.jpg)
OverviewOverview
Primary StructurePrimary StructureSecondary StructureSecondary StructureTertiary StructureTertiary StructureQuaternary StructureQuaternary Structure
![Page 4: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/4.jpg)
Primary StructurePrimary Structure
Polypeptide chains Polypeptide chains Amino Amino AcidsAcidsLargest polypeptide chain Largest polypeptide chain approx has 5000AA but most approx has 5000AA but most have less than 2000AAhave less than 2000AAAmino Acid Basic Structure Amino Acid Basic Structure HH22NN--CHCH--COOHCOOHArrangement of the 20 Arrangement of the 20 amino acids in the amino acids in the polypeptide is the amino acid polypeptide is the amino acid sequence which composes sequence which composes the primary structure of the the primary structure of the proteinprotein
National Genome Research Institutegenome.gov
![Page 5: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/5.jpg)
http://www.people.virginia.edu/~rjh9u/aminacid.html
20 Amino Acids
Nonpolar,hydrophobic
Polar, uncharged
Polar, charged
![Page 6: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/6.jpg)
Amino Acid ClassificationAmino Acid Classification
Bioinformatics Methods II, Spring 2003
HK R
ED
F YW
IL V
M
A
Q
S N
T
CH
G PCS-S
polar
positive
negative
charged
beta-branched
aliphatic
aromatic
hydrophobic
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.
![Page 7: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/7.jpg)
StereochemistryStereochemistry
Configuration of amino acids in proteinsConfiguration of amino acids in proteinsThe CORN LawThe CORN Law
![Page 8: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/8.jpg)
Bond FormationBond Formation
Linking two amino acids Linking two amino acids togethertogether
Definitions (NDefinitions (N--terminal, terminal, CC--terminal, polypeptide terminal, polypeptide backbone, amino acid backbone, amino acid residue, side chains)residue, side chains)
http://web.mit.edu/esgbio/www/lm/proteins/peptidebond.html
![Page 9: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/9.jpg)
Primary StructurePrimary Structure
What is a native protein?What is a native protein?Protein conformation & problem of protein Protein conformation & problem of protein foldingfolding
Hydrophobic, hydrophilicHydrophobic, hydrophilicChargeChargeChaperonesChaperones
![Page 10: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/10.jpg)
Special Purpose Amino AcidsSpecial Purpose Amino Acids
ProlineProline
CysteineCysteine
![Page 11: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/11.jpg)
IntroductionIntroductionPeptide bond geometryPeptide bond geometryRamachandranRamachandran plotplotStructuresStructures
Protein Secondary StructureProtein Secondary Structure
![Page 12: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/12.jpg)
Regular local structures formed by single strands Regular local structures formed by single strands of peptide chain due to constraints on backbone of peptide chain due to constraints on backbone conformationconformation
![Page 13: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/13.jpg)
Peptide BondPeptide Bond
http://cmgm.stanford.edu/biochem/biochem201/Slides/
![Page 14: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/14.jpg)
Peptide Bond Peptide Bond
Resonance Resonance CC--N bond length of the peptide is 10% shorter N bond length of the peptide is 10% shorter than that found in usual Cthan that found in usual C--N amine bondsN amine bondsPeptide bond planer Peptide bond planer ωω, angle around peptide bond, , angle around peptide bond, 0000 for for ciscis, 180, 18000 for transfor trans
![Page 15: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/15.jpg)
RamachandranRamachandran PlotPlot
http://hykim.chungbuk.ac.kr/lectures/biochem/4-5/fig6-9(L).jpg
![Page 16: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/16.jpg)
Alpha HelixAlpha Helix
http://cmgm.stanford.edu/biochem/biochem201/Slides/
![Page 17: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/17.jpg)
Alpha HelixAlpha Helix
LeftLeft--handedhanded RightRight--handedhanded
http://www.rtc.riken.go.jp
![Page 18: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/18.jpg)
Alpha Structure FeaturesAlpha Structure Features
3.6 residues per turn3.6 residues per turn5.4 angstroms in length per turn5.4 angstroms in length per turncarboxyl group of residue i hydrogen bonds to carboxyl group of residue i hydrogen bonds to amino group of residue i+4amino group of residue i+4
![Page 19: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/19.jpg)
Helix StructuresHelix Structures
Φ ψ H Bond R/t A/tΦ ψ H Bond R/t A/tAlpha Alpha --57.8 57.8 --47 i, i + 4 3.6 1347 i, i + 4 3.6 13
33--10 Helix 10 Helix --49 49 --26 i, i + 3 3.0 1026 i, i + 3 3.0 10
Pi Helix Pi Helix --57 57 --80 i , i + 5 4.4 1680 i , i + 5 4.4 16
http://broccoli.mfn.ki.se
![Page 20: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/20.jpg)
More Helix StructuresMore Helix Structures
TypeType ΦΦ ψψ commentscomments
CollagenCollagen --5151 153153 Fibrous proteinsFibrous proteinsThree left handed Three left handed helicieshelicies((GlyXY)nGlyXY)n, X Y = Pro / , X Y = Pro / LysLys
Type II helicesType II helices --7979 150150 leftleft--handed handed helicieshelicies formed formed by by polyglycinepolyglycine
![Page 21: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/21.jpg)
Beta Sheet Beta Sheet
http://www.rothamsted.bbsrc.ac.uk/notebook/courses/guide/images/sheet.gif
![Page 22: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/22.jpg)
Beta Sheet FeaturesBeta Sheet Features
Sheets can be made up of any number of strandsSheets can be made up of any number of strandsOrientation and hydrogen bonding pattern of Orientation and hydrogen bonding pattern of strands gives rise to flat or twisted sheetsstrands gives rise to flat or twisted sheetsParallel sheets buried inside, while Parallel sheets buried inside, while AntiparallelAntiparallelsheets occurs on the surfacesheets occurs on the surface
![Page 23: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/23.jpg)
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
![Page 24: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/24.jpg)
Beta turnsBeta turns
i + 1 Pro
i + 2 Pro or Gly
i + 3 Gly
http://rayl0.bio.uci.edu/~mjhsieh/sstour/image/betaturn.png
![Page 25: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/25.jpg)
![Page 26: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/26.jpg)
Interactions Interactions
Covalent bondsCovalent bondsDisulphide bond (2.2 Disulphide bond (2.2 00A) between two A) between two CysCys residuesresidues
NonNon--covalent bondscovalent bondsLong range electrostatic interactionLong range electrostatic interactionShort range (4 Short range (4 00A) van A) van derder WaalsWaals interactioninteractionHydrogen bond (3 Hydrogen bond (3 00A)A)
![Page 27: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/27.jpg)
Tertiary Protein StructureTertiary Protein Structure
Defines the three dimensional conformation of Defines the three dimensional conformation of an entire peptide chain in spacean entire peptide chain in spaceDetermined by the primary structureDetermined by the primary structureModular in natureModular in nature
![Page 28: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/28.jpg)
Aspects which determine tertiary Aspects which determine tertiary structurestructure
Covalent disulfide bonds from between closely Covalent disulfide bonds from between closely aligned aligned cysteinecysteine residues form the unique Amino residues form the unique Amino Acid Acid cystinecystine..Nearly all of the polar, hydrophilic R groups are Nearly all of the polar, hydrophilic R groups are located in the surface, where they may interact located in the surface, where they may interact with waterwith waterThe The nonpolarnonpolar, , hydropobichydropobic R groups are usually R groups are usually located inside the moleculelocated inside the molecule
![Page 29: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/29.jpg)
Motifs and DomainsMotifs and Domains
Motif Motif –– a small structural domain that can be a small structural domain that can be recognized in a variety of proteinsrecognized in a variety of proteinsDomain Domain –– Portion of a protein that has a tertiary Portion of a protein that has a tertiary structure of its own. In larger proteins each structure of its own. In larger proteins each domain is connected to other domains by short domain is connected to other domains by short flexible regions of polypeptide. flexible regions of polypeptide.
![Page 30: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/30.jpg)
![Page 31: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/31.jpg)
![Page 32: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/32.jpg)
![Page 33: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/33.jpg)
![Page 34: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/34.jpg)
![Page 35: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/35.jpg)
Modular Nature of Modular Nature of ProtiensProtiens
Epidermal Growth Epidermal Growth Factor (EGF) domain is Factor (EGF) domain is a module present in a module present in several different proteins several different proteins illustrated here in orange.illustrated here in orange.Each color represents a Each color represents a different domaindifferent domain
![Page 36: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/36.jpg)
Domain ShufflingDomain Shuffling
Occurs in evolutionOccurs in evolutionNew proteins arise by joining of New proteins arise by joining of preexistingpreexistingprotein domain or modules.protein domain or modules.
![Page 37: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/37.jpg)
Quaternary StructureQuaternary Structure
Not all proteins have a Not all proteins have a quaternary structurequaternary structureA composite of multiple A composite of multiple polypoly--peptide chains is peptide chains is called an called an oligomeroligomer or or multimericmultimericHemoglobin is an Hemoglobin is an example of a tetramerexample of a tetramerGlobular vs. FibrousGlobular vs. Fibrous
![Page 38: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/38.jpg)
Protein FoldingProtein Folding
Protein folding constitutes the process by which Protein folding constitutes the process by which a polya poly--peptide chain reduces its free energy by peptide chain reduces its free energy by taking a secondary, tertiary, and possibly a taking a secondary, tertiary, and possibly a quaternary structurequaternary structure
![Page 39: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/39.jpg)
ThermodynamicsThermodynamics
Proteins follow Proteins follow spontaneous reactions to spontaneous reactions to reach the conformation reach the conformation of lowest free energyof lowest free energyReaction spontaneity is Reaction spontaneity is modeled by the equation modeled by the equation ∆∆G= G= ∆∆HH--TT∆∆S S
![Page 40: Protein Structure Basics - Virginia Techchekhov.cs.vt.edu/2004/presentations/hinges_protein... · 2004-04-29 · Primary Structure Polypeptide chains ÆAmino Acids Largest polypeptide](https://reader035.fdocuments.us/reader035/viewer/2022081517/5ede1fd2ad6a402d66696a04/html5/thumbnails/40.jpg)
Molecular VisualizationMolecular Visualization
Goal: Clear visualization of Goal: Clear visualization of molecular structuremolecular structureDifferent visualization modes Different visualization modes elucidate different molecular elucidate different molecular propertiespropertiesSome representations include Some representations include Ribbons, Ribbons, SpaceFillSpaceFill and and BackboneBackbone