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Outline

Protein structure
Primary Secondary Tertiary Quaternary

Fundamentals of Protein Structure


Thomas Funkhouser Princeton University CS597A, Fall 2007

Levels of Protein Structure

Outline
Protein structure
Primary Secondary Tertiary Quaternary

Lehninger Principles of Biochemistry (3rd edition) David L. Nelson, Michael M. Cox

Primary Structure
DNA
GGGGCTACGGGGGGTGGGGCTTCGCGCCCCGCCGGCCTAIAAGCGGGCCGCCGCGGCTCCGTGCCQTTGCCGACCTTGCCT GcCGCCGCTGCTGCTTCGCGCCCGTCGCCTCCGCCATGGCTCCCAGGAAGTTCTTCGTGGGTGGCAACTGGAAGATGAACG GCGACAAGAAGAGCTTGGGCGAGCTCATCCACACGCTGAATGGCGCCAAGCTCTCGGCCGACACCGAGGTGGTTTGCGGAG CCCCTTCAATCTACCTTGATTTTGCCCGCCAGAAGCTTGATGCAAAGATTGGAGTTGCAGCACAAAACTGTTACAACGTAC CGAAGGGTGCTTTCACAGGAGAGATCAGCCCAGCAATGATCAAAGATATTGGAGCTGCATGGGTGATCCTGGGCCACTCAG AGCGGAGGCATGTTTTTGGAGAGTCTGATGAGTTGATTGGGCAGAAGGTGGCTCATGCTCMTGCTGAAGGC .[Straus85] . .

Primary Structure
Transcription and translation (DNAProtein)

Sequence of Nucleic Acids

http://www.accessexcellence.org

Primary Structure
Transcription and translation (DNAProtein)
First Position | U(T) Second Position Third ------------------------------------ Position U(T) C A G | Phe Phe Leu Leu Leu Leu Leu Leu Ile Ile Ile Met Val Val Val Val Ser Ser Ser Ser Pro Pro Pro Pro Thr Thr Thr Thr Ala Ala Ala Ala Tyr Tyr STOP STOP His His Gln Gln Asn Asn Lys Lys Asp Asp Glu Glu Cys Cys STOP Trp Arg Arg Arg Arg Ser Ser Arg Arg Gly Gly Gly Gly U(T) C A G U(T) C A G U(T) C A G U(T) C A G

Primary Structure
Transcription and translation (DNAProtein)
Alanine Cysteine Aspartic Acid Glutamic Acid Phenylalanine Glycine Histidine Isoleucine Lysine Leucine Methionine Asparagine Proline Glutamine Arginine Serine Threonine Valine Tryptophan Tyrosine Ala Cys Asp Glu Phe Gly His Ile Lys Leu Met Asn Pro Gln Arg Ser Thr Val Trp Tyr A C D E F G H I K L M N P Q R S T V W Y

Short-hand Names for Amino Acids

Primary Structure
Transcription and translation (DNAProtein)
GGGGCTACGGGGGGTGGGGCTTCGCGCCCCGCCGGCCTAIAAGCGGGCCGCCGCGGCTCCGTGCCQTTGCCGACCTTGCCT GcCGCCGCTGCTGCTTCGCGCCCGTCGCCTCCGCCATGGCTCCCAGGAAGTTCTTCGTGGGTGGCAACTGGAAGATGAACG GCGACAAGAAGAGCTTGGGCGAGCTCATCCACACGCTGAATGGCGCCAAGCTCTCGGCCGACACCGAGGTGGTTTGCGGAG CCCCTTCAATCTACCTTGATTTTGCCCGCCAGAAGCTTGATGCAAAGATTGGAGTTGCAGCACAAAACTGTTACAACGTAC CGAAGGGTGCTTTCACAGGAGAGATCAGCCCAGCAATGATCAAAGATATTGGAGCTGCATGGGTGATCCTGGGCCACTCAG AGCGGAGGCATGTTTTTGGAGAGTCTGATGAGTTGATTGGGCAGAAGGTGGCTCATGCTCMTGCTGAAGGC . . .

Primary Structure
Transcription and translation (DNAProtein)
GGGGCTACGGGGGGTGGGGCTTCGCGCCCCGCCGGCCTAIAAGCGGGCCGCCGCGGCTCCGTGCCQTTGCCGACCTTGCCT GcCGCCGCTGCTGCTTCGCGCCCGTCGCCTCCGCCATGGCTCCCAGGAAGTTCTTCGTGGGTGGCAACTGGAAGATGAACG GCGACAAGAAGAGCTTGGGCGAGCTCATCCACACGCTGAATGGCGCCAAGCTCTCGGCCGACACCGAGGTGGTTTGCGGAG CCCCTTCAATCTACCTTGATTTTGCCCGCCAGAAGCTTGATGCAAAGATTGGAGTTGCAGCACAAAACTGTTACAACGTAC CGAAGGGTGCTTTCACAGGAGAGATCAGCCCAGCAATGATCAAAGATATTGGAGCTGCATGGGTGATCCTGGGCCACTCAG AGCGGAGGCATGTTTTTGGAGAGTCTGATGAGTTGATTGGGCAGAAGGTGGCTCATGCTCMTGCTGAAGGC . . .

Sequence of Nucleic Acids

Sequence of Nucleotides

APRKFFVGGNWKMNGDKKSLGELIHTLNGAKLSADTEVVCGAPSIYLDFAR QKLDAKIGVAAQNCYKVPKGAFTGEISPAMIKDIGAAWVILGHSERRHVFGES DELIGQKVAHALAEGLGVIACIGEKLDEREAGITEKVVFEQTKAIADNVKDW SKVVLAYEPVWAIGTGKTATPQQAQEVHEKLRGWLKSHVSDAVAQSTRI IYGGSVTGGNCKELASQHDVDGFLVGGASLKPEFVDIINAKH

APRKFFVGGNWKMNGDKKSLGELIHTLNGAKLSADTEVVCGAPSIYLDFAR QKLDAKIGVAAQNCYKVPKGAFTGEISPAMIKDIGAAWVILGHSERRHVFGES DELIGQKVAHALAEGLGVIACIGEKLDEREAGITEKVVFEQTKAIADNVKDW SKVVLAYEPVWAIGTGKTATPQQAQEVHEKLRGWLKSHVSDAVAQSTRI IYGGSVTGGNCKELASQHDVDGFLVGGASLKPEFVDIINAKH

Sequence of Amino Acids


[Straus85]

Sequence of Amino Acids


[Straus85]

Primary Structure
Transcription and translation (DNAProtein)
GGGGCTACGGGGGGTGGGGCTTCGCGCCCCGCCGGCCTAIAAGCGGGCCGCCGCGGCTCCGTGCCQTTGCCGACCTTGCCT GcCGCCGCTGCTGCTTCGCGCCCGTCGCCTCCGCCATGGCTCCCAGGAAGTTCTTCGTGGGTGGCAACTGGAAGATGAACG GCGACAAGAAGAGCTTGGGCGAGCTCATCCACACGCTGAATGGCGCCAAGCTCTCGGCCGACACCGAGGTGGTTTGCGGAG CCCCTTCAATCTACCTTGATTTTGCCCGCCAGAAGCTTGATGCAAAGATTGGAGTTGCAGCACAAAACTGTTACAACGTAC CGAAGGGTGCTTTCACAGGAGAGATCAGCCCAGCAATGATCAAAGATATTGGAGCTGCATGGGTGATCCTGGGCCACTCAG AGCGGAGGCATGTTTTTGGAGAGTCTGATGAGTTGATTGGGCAGAAGGTGGCTCATGCTCMTGCTGAAGGC . . .

Primary Structure
Transcription and translation (DNAProtein)
GGGGCTACGGGGGGTGGGGCTTCGCGCCCCGCCGGCCTAIAAGCGGGCCGCCGCGGCTCCGTGCCQTTGCCGACCTTGCCT GcCGCCGCTGCTGCTTCGCGCCCGTCGCCTCCGCCATGGCTCCCAGGAAGTTCTTCGTGGGTGGCAACTGGAAGATGAACG GCGACAAGAAGAGCTTGGGCGAGCTCATCCACACGCTGAATGGCGCCAAGCTCTCGGCCGACACCGAGGTGGTTTGCGGAG CCCCTTCAATCTACCTTGATTTTGCCCGCCAGAAGCTTGATGCAAAGATTGGAGTTGCAGCACAAAACTGTTACAACGTAC CGAAGGGTGCTTTCACAGGAGAGATCAGCCCAGCAATGATCAAAGATATTGGAGCTGCATGGGTGATCCTGGGCCACTCAG AGCGGAGGCATGTTTTTGGAGAGTCTGATGAGTTGATTGGGCAGAAGGTGGCTCATGCTCMTGCTGAAGGC . . .

Sequence of Nucleotides

Sequence of Nucleotides

APRKFFVGGNWKMNGDKKSLGELIHTLNGAKLSADTEVVCGAPSIYLDFAR QKLDAKIGVAAQNCYKVPKGAFTGEISPAMIKDIGAAWVILGHSERRHVFGES DELIGQKVAHALAEGLGVIACIGEKLDEREAGITEKVVFEQTKAIADNVKDW SKVVLAYEPVWAIGTGKTATPQQAQEVHEKLRGWLKSHVSDAVAQSTRI IYGGSVTGGNCKELASQHDVDGFLVGGASLKPEFVDIINAKH

APRKFFVGGNWKMNGDKKSLGELIHTLNGAKLSADTEVVCGAPSIYLDFAR QKLDAKIGVAAQNCYKVPKGAFTGEISPAMIKDIGAAWVILGHSERRHVFGES DELIGQKVAHALAEGLGVIACIGEKLDEREAGITEKVVFEQTKAIADNVKDW SKVVLAYEPVWAIGTGKTATPQQAQEVHEKLRGWLKSHVSDAVAQSTRI IYGGSVTGGNCKELASQHDVDGFLVGGASLKPEFVDIINAKH

Sequence of Amino Acids


[Straus85]

Sequence of Amino Acids


[Straus85]

Primary Structure
Amino acid:
(Amino group) (Carboxyl group)

Primary Structure
Twenty amino acids:

(Alpha carbon)

OH

(Side chain)

[http://www.cryst.bbk.ac.uk]

[http://www.cryst.bbk.ac.uk]

Primary Structure
Amino acids are linked by peptide bonds

Primary Structure
Polypeptide chain:

Lehninger Principles of Biochemistry (3rd edition) David L. Nelson, Michael M. Cox

Biochemistry (5th edition) Jeremy M. Berg, John L. Tymoczko, Lubert Stryer

APRKFFVGGNWKMNGDKKSLGELIHTLNGAKLSADTEVVCGAPSIYLDFAR QKLDAKIGVAAQNCYKVPKGAFTGEISPAMIKDIGAAWVILGHSERRHVFGES DELIGQKVAHALAEGLGVIACIGEKLDEREAGITEKVVFEQTKAIADNVKDW SKVVLAYEPVWAIGTGKTATPQQAQEVHEKLRGWLKSHVSDAVAQSTRI IYGGSVTGGNCKELASQHDVDGFLVGGASLKPEFVDIINAKH

Sequence of Amino Acids

[http://www.cryst.bbk.ac.uk]

Primary Structure
Polypeptide chain:
Backbone

Primary Structure
Polypeptide chain:

Side chain

APRKFFVGGNWKMNGDKKSLGELIHTLNGAKLSADTEVVCGAPSIYLDFAR QKLDAKIGVAAQNCYKVPKGAFTGEISPAMIKDIGAAWVILGHSERRHVFGES DELIGQKVAHALAEGLGVIACIGEKLDEREAGITEKVVFEQTKAIADNVKDW SKVVLAYEPVWAIGTGKTATPQQAQEVHEKLRGWLKSHVSDAVAQSTRI IYGGSVTGGNCKELASQHDVDGFLVGGASLKPEFVDIINAKH

APRKFFVGGNWKMNGDKKSLGELIHTLNGAKLSADTEVVCGAPSIYLDFAR QKLDAKIGVAAQNCYKVPKGAFTGEISPAMIKDIGAAWVILGHSERRHVFGES DELIGQKVAHALAEGLGVIACIGEKLDEREAGITEKVVFEQTKAIADNVKDW SKVVLAYEPVWAIGTGKTATPQQAQEVHEKLRGWLKSHVSDAVAQSTRI IYGGSVTGGNCKELASQHDVDGFLVGGASLKPEFVDIINAKH

Sequence of Amino Acids

[http://www.cryst.bbk.ac.uk]

Sequence of Amino Acids

[http://www.cryst.bbk.ac.uk]

Primary Structure
Polypeptide chain:
Side chain

Primary Structure
Polypeptide chain:

Side chain

APRKFFVGGNWKMNGDKKSLGELIHTLNGAKLSADTEVVCGAPSIYLDFAR QKLDAKIGVAAQNCYKVPKGAFTGEISPAMIKDIGAAWVILGHSERRHVFGES DELIGQKVAHALAEGLGVIACIGEKLDEREAGITEKVVFEQTKAIADNVKDW SKVVLAYEPVWAIGTGKTATPQQAQEVHEKLRGWLKSHVSDAVAQSTRI IYGGSVTGGNCKELASQHDVDGFLVGGASLKPEFVDIINAKH

APRKFFVGGNWKMNGDKKSLGELIHTLNGAKLSADTEVVCGAPSIYLDFAR QKLDAKIGVAAQNCYKVPKGAFTGEISPAMIKDIGAAWVILGHSERRHVFGES DELIGQKVAHALAEGLGVIACIGEKLDEREAGITEKVVFEQTKAIADNVKDW SKVVLAYEPVWAIGTGKTATPQQAQEVHEKLRGWLKSHVSDAVAQSTRI IYGGSVTGGNCKELASQHDVDGFLVGGASLKPEFVDIINAKH

Sequence of Amino Acids

[http://www.cryst.bbk.ac.uk]

Sequence of Amino Acids

[http://www.cryst.bbk.ac.uk]

Primary Structure
Peptide bond:

Primary Structure
Peptide bond:

omega

Most bond angles are constrained

Peptides have at most two free torsion angles (omega is 180 (trans) or 0 cis)
[http://www.cryst.bbk.ac.uk] [http://www.cryst.bbk.ac.uk]

Primary Structure
N-C and C -C bonds can rotate

Primary Structure
Ramachandran plot:

Lehninger Principles of Biochemistry (3rd edition) David L. Nelson, Michael M. Cox

[PDBSUM]

1tim

Primary Structure
Important properties of amino acids:
Size Charge Polarity Aromaticity Hydrophobicity Conformational constraints

Primary Structure
Important properties of amino acids:
Size Charge Polarity Aromaticity Hydrophobicity Conformational constraints

[http://www.cryst.bbk.ac.uk]

Primary Structure
Important properties of amino acids:
Size Charge Polarity Aromaticity Hydrophobicity Conformational constraints

Primary Structure
Important properties of amino acids:
Size Charge Polarity Aromaticity Hydrophobicity Conformational constraints

[http://www.cryst.bbk.ac.uk]

[http://www.cryst.bbk.ac.uk]

Primary Structure
Important properties of amino acids:
Size Charge Polarity Aromaticity Hydrophobicity Conformational constraints

Primary Structure
Important properties of amino acids:
Size Charge Polarity Aromaticity Hydrophobicity Conformational constraints

[http://www.cryst.bbk.ac.uk]

[http://www.cryst.bbk.ac.uk]

Primary Structure
Important properties of amino acids:
Size Charge Polarity Aromaticity Hydrophobicity Conformational constraints

Structure
Forces affecting structure:
H-bonding Van der Waals Electrostatics Hydrophobicity Disulfide Bridges
+

H-bonds form when a hydrogen is shared by two partially negatively charged atoms
In proteins, the participating atoms are always N/N, O/O, or N/O, usually in polar residues or backbone
[http://www.cryst.bbk.ac.uk]

Structure
Forces affecting structure:
H-bonding Van der Waals Electrostatics Hydrophobicity Disulfide Bridges Van de Waals forces are caused by fluctuation in the positions of electrons on uncharged atoms They are repulsive or attractive, depending on the proximity of interacting atoms

Structure
Forces affecting structure:
H-bonding Van der Waals Electrostatics Hydrophobicity Disulfide Bridges

http://honiglab.cpmc.columbia.edu/grasp/pictures.html

Structure
Forces affecting structure:
H-bonding Van der Waals Electrostatics Hydrophobicity Disulfide Bridges

Structure
Forces affecting structure:
H-bonding Van der Waals Electrostatics Hydrophobicity Disulfide Bridges

Hydrophobic (nonpolar) resiidues generally pack together away from polar solutions (water)
e.g., in core of proteins in water, in binding sites, on the surface of proteins in membranes, etc.

Cysteines can be oxidized to form covalent S-S bonds between amino acids distant in primary sequence

Outline
Protein structure
Primary Secondary Tertiary Quaternary

Secondary Structure
Loop

Alpha Helix Beta Sheet


1tim

[Jena]

Secondary Structure
Some repeating sequences of torsion angles are very stable
Alpha helix Beta sheet

Secondary Structure
Some repeating sequences of torsion angles are very stable
Alpha helix Beta sheet

[http://www.cryst.bbk.ac.uk]

[http://www.cryst.bbk.ac.uk]

Secondary Structure
Some repeating sequences of torsion angles are very stable
Alpha helix Beta sheet

Secondary Structure
Some repeating sequences of torsion angles are very stable
Alpha helix Beta sheet

[http://www.cryst.bbk.ac.uk]

Lehninger Principles of Biochemistry (3rd edition) David L. Nelson, Michael M. Cox

[chemed.chem.purdue.edu]

Secondary Structure
Some repeating sequences of torsion angles are very stable
Alpha helix Beta sheet

Secondary Structure
Some repeating sequences of torsion angles are very stable
Alpha helix Beta sheet

[http://www.cryst.bbk.ac.uk]

[http://www.cryst.bbk.ac.uk]

Secondary Structure
Some repeating sequences of torsion angles are very stable
Alpha helix Beta sheet

Secondary Structure
Some repeating sequences of torsion angles are very stable
Alpha helix Beta sheet

[http://www.cryst.bbk.ac.uk]

[http://www.cryst.bbk.ac.uk]

Secondary Structure
Some repeating sequences of torsion angles are very stable
Alpha helix Beta sheet

Secondary Structure
Some repeating sequences of torsion angles are very stable
Alpha helix Beta sheet

[chemed.chem.purdue.edu]

Antiparallel

Parallel
[http://www.cryst.bbk.ac.uk]

Secondary Structure
Some repeating sequences of torsion angles are very stable
Alpha helix Beta sheet

Secondary Structure
Some repeating sequences of torsion angles are very stable
Alpha helix Beta sheet

Parallel
Lehninger Principles of Biochemistry (3rd edition) David L. Nelson, Michael M. Cox

AntiParallel

[http://www.cryst.bbk.ac.uk]

Secondary Structure
Others form loops, turns etc.

Secondary Structure
Others form loops, turns etc.

Lehninger Principles of Biochemistry (3rd edition) David L. Nelson, Michael M. Cox

[PDBSUM]

Secondary Structure
Others form loops, turns etc.

Supersecondary structure / motifs

Helix loop helix

Helix loop helix Calcium-binding motif

[http://www.cryst.bbk.ac.uk]

Introduction to protein structure (2nd edition) Carl Branden, John Tooze

Supersecondary structure / motifs

Supersecondary structure / motifs


Four classes:

Geek Key motif

All All / +

- - motif

Hairpin motif

Introduction to protein structure (2nd edition) Carl Branden, John Tooze

Introduction to protein structure (2nd edition) Carl Branden, John Tooze

Secondary Structure Visualization

Secondary Structure Visualization


Loop

Beta Sheet

Outline
Protein structure
Primary Secondary Tertiary Quaternary

Tertiary Structure
Arrangement of atoms:

Alpha Helix
1tim

[Jena]

[pymol]

1atp

10

Tertiary Structure
How protein folds:

Tertiary Structure
How protein folds:

[pymol]

1atp

[pymol]

1atp

Tertiary Structure

Tertiary Structure
Function Structural classifications
Fold similarities Evolutionary relationships Sequence similarities

Sequence

Structure

Examples:
CATH SCOP

The globin fold is resilient to amino acid changes. V. stercoraria (bacterial) hemoglobin (left) and P. marinus (eukaryotic) hemoglobin (right) share just 8% sequence identity, but their overall fold and function is identical.
Slide courtesy of Philip Bourne

Tertiary Structure
CATH hierarchy:
Class Architecture Topology Homology S35 (Family) S95 S100

Tertiary Structure
SCOP hierarchy:
Class Fold Superfamily Family Protein Domain Species PDB
SCOP: 1gsa
1. Root: scop 2. Class: Alpha and beta proteins (a/b) [51349] 3. Fold: PreATP-grasp domain [52439] 4. Superfamily: PreATP-grasp domain [52440] 5. Family: Prokaryotic glutathione synthetase, N-terminal domain [52457] 6. Protein: Prokaryotic glutathione synthetase, N-terminal domain [52458] 7. Species: Escherichia coli [52459] http://scop.mrc-lmb.cam.ac.uk/scop/ [Murzin95]

Structural Layout

http://cathwww.biochem.ucl.ac.uk/ [Orengo97]

11

Tertiary Structure
SCOP hierarchy:
7 945 1,539 2,845 70,859 SCOP: Structural Classification of Proteins (1.69 release)

Outline
Protein structure
Primary Secondary Tertiary Quaternary

Quatenary Structure
How multiple chains/proteins form a complex:

Quatenary Structure
How multiple chains/proteins form a complex:

Active binding site may be at interface between two chains

[Rasurf]

1tim

[Rasurf]

1tim

Quatenary Structure
How multiple chains/proteins form a complex:
Chain may take a new (active) conformation when bound to another

Quaternary structure

[Rasurf]

1tim

Ribbon diagram of a heptameric, 63 kDa cleavage fragment (PA63) of the protective antigen (PA) protein, produced by Bacillus anthracis as part of the anthrax toxin. The quaternary structure is that of a pre-pore, which later forms a channel that allows other toxins into the cytosol of the target cell, so the pathogen can cause damage to the host. [http://www3.niaid.nih.gov/]

12

Quaternary structure

Protein Structure Level Summary


Protein structure description

Primary Secondary Tertiary Quaternary

amino acid sequence local fold pattern of small subsequence fold of entire protein chain complex of multiple chains

Quorum Sensing Activity in Vibrio harveyi [Megan Pomianek, Chemistry, Princeton University]

Lehninger Principles of Biochemistry (3rd edition) David L. Nelson, Michael M. Cox

Protein Structure Databases


Repositories:

Protein Structure Databases


Repositories:
Primary Secondary Tertiary Quaternary UniProt DSSP PDB PQS
Chain 1GSA:_ Compound Glutathione Synthetase Type Protein Molecular Weight 35547 Number of Residues 316 Number of Alpha 9 Content of Alpha 27.22 Number of Beta 19 Content of Beta 28.16
1 MIKLGIVMDP IANINIKKDS SFAMLLEAQR RGYELHYMEM GDLYLINGEA EEEEE S GGGTTTTTTH HHHHHHHHHH HT EEEEE G GGEEEETTEE

Protein Structure Databases


Repositories:

Primary Secondary Tertiary Quaternary

Primary Secondary Tertiary Quaternary

UniProt DSSP PDB PQS

Chain 1GSA:_ Compound Glutathione Synthetase Type Protein Molecular Weight 35547 Number of Residues 316

1 MIKLGIVMDP IANINIKKDS SFAMLLEAQR RGYELHYMEM GDLYLINGEA

51 RAHTRTLNVK QNYEEWFSFV GEQDLPLADL DVILMRKDPP FDTEFIYATY

51 RAHTRTLNVK QNYEEWFSFV GEQDLPLADL DVILMRKDPP FDTEFIYATY EEEEEEEEE S SS EEE EEEEEGGGS SEEEE HHHHHHHH

101 ILERAEEKGT LIVNKPQSLR DCNEKLFTAW FSDLTPETLV TRNKAQLKAF

101 ILERAEEKGT LIVNKPQSLR DCNEKLFTAW FSDLTPETLV TRNKAQLKAF HHHHHHHTT EEES HHHHH HTTTTGGGGG GTTTB EEE ES HHHHHHH

151 WEKHSDIILK PLDGMGGASI FRVKEGDPNL GVIAETLTEH GTRYCMAQNY

201 LPAIKDGDKR VLVVDGEPVP YCLARIPQGG ETRGNLAAGG RGEPRPLTES

251 DWKIARQIGP TLKEKGLIFV GLDIIGDRLT EINVTSPTCI REIEAEFPVS

H = helix B = residue in isolated beta bridge E = extended beta strand G = 310 helix T = hydrogen bonded turn S = bend

151 WEKHSDIILK PLDGMGGASI FRVKEGDPNL GVIAETLTEH GTRYCMAQNY HHHHSSEEEE SS TTTT EEE TTTTTH HHHHHHHTTT TTS EEEEE

201 LPAIKDGDKR VLVVDGEPVP YCLARIPQGG ETRGNLAAGG RGEPRPLTES GGGGG EEE EEEETTEE S EEEEEE SS S GGGT EEEEEE HH

251 DWKIARQIGP TLKEKGLIFV GLDIIGDRLT EINVTSPTCI REIEAEFPVS HHHHHHHHHT HHHHTT EE EEEEETTEE EEE SS H HHHHHHSS

301 ITGMLMDAIE ARLQQQ

301 ITGMLMDAIE ARLQQQ HHHHHHHHHH HHT

http://www.uniprot.org/ [Apweiler04]

[Kabsch83]

Protein Structure Databases


Repositories:
Primary Secondary Tertiary Quaternary UniProt DSSP PDB PQS

UniProt DSSP PDB PQS

[Kabsch83]

http://www.rcsb.org/pdb/ [Berman00]

13

Protein Structure Databases


Repositories:

Summary
Protein structure description

References
Information and figures were taken from:
Introduction to protein structure (2nd edition)
Carl Branden, John Tooze

Lehninger Principles of Biochemistry (3rd edition)


David L. Nelson, Michael M. Cox

Biochemistry (5th edition)


Jeremy M. Berg, John L. Tymoczko, Lubert Stryer

http://www.cs.cryst.bbk.ac.uk http://www.accessexcellence.org http://chemmed.chem.purdue.edu

Example: Hemoglobin
Chain A Tertiary Structure

Deoxyhemoglobin (alpha chain). Chain: a. Engineered: yes. Mutation: yes. Deoxyhemoglobin (beta chain). Chain: b, d. Engineered: yes. Mutation: yes 1C7D E.A.Brucker

Primary Secondary Tertiary Quaternary

UniProt DSSP PDB PQS

Primary Secondary Tertiary Quaternary

amino acid sequence local fold pattern of small subsequence fold of entire protein chain complex of multiple chains

Protein folding/binding

http://pqs.ebi.ac.uk/ [Hendrick98]

Disulfide linkages Hydrogen bonding Electrostatic interactions Hydrophobic interactions Van der Waals forces
[Jena]

1tim

Example: Hemoglobin
Chain A Primary structure: 284 residues

Chain A Secondary structure and motifs: 19 Helices 50 Helices-helices interacs 14 Beta turns 2 gamma turns

Deoxyhemoglobin (alpha chain). Chain: a. Engineered: yes. Mutation: yes. Deoxyhemoglobin (beta chain). Chain: b, d. Engineered: yes. Mutation: yes 1C7D E.A.Brucker

Example: Hemoglobin

Deoxyhemoglobin Quaternary Structure

Deoxyhemoglobin (alpha chain). Chain: a. Engineered: yes. Mutation: yes. Deoxyhemoglobin (beta chain). Chain: b, d. Engineered: yes. Mutation: yes 1C7D E.A.Brucker

14