Protein Structure and Function

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Protein Structure and Function

• 1?, 2 ?, 3 ?, 4 ? Structure
• Viewing, interpreting structure
• Protein Characterization

BIO520 Bioinformatics Jim Lund
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Protein variety

• 100 to gt10,000 aa
• Soluble
• Integral membrane proteins
• Membrane-associated
• Single domain, multiple domains
• singular, multimeric, large complex

DIVERSE
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Protein Structure

• 1? structure
• aa sequence
• 2 ? structure
• regular local folding
• 3 ? structure
• packing and overall folding
• 4 ? structure
• polypeptidepolypeptide interaction

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(No Transcript)
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Modifications

• Proteolysis/processing
• Residues Modified
• cysteine disulfides
• phosphorylation
• methylation
• Heteroatoms
• Metal ions, heme, cofactors.

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Dogma
SequenceStructure
Similar Sequence
Similar Function
Kinetics vs Thermodynamics Chaperones
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?,? angles

• Restricted, but considerable rotation
• Different residues?different ?,?
• Regular ?,?
• ? helix
• ? sheet

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Experimental ?,? angles
Hovmöller et al., 2002. Conformations of amino
acids in proteins
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Forces

• H-bonding
• orientation (dielectric)
• Hydrophobic effect
• nonpolar to core
• Ionic interaction
• to -, (dielectric)
• Dipole effects
• ? helix, N to C ( to -)

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??-helix

• right-handed
• aa preferences
• A,E,L,M (enriched)
• P,G,Y,S (less likely)
• 3.6 residues/turn
• helical wheel (amphipathic)
• dipole N to C

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?-sheet

• Parallel or antiparallel N-to-C
• Mixed ?-sheets are rare only 20 of ?-sheets
  are mixed parallel/anti-parallel.
• pleated and twisted
• aa preferences

"Super"secondary
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?-turn, loops

• Length, conformation variable
• 2 aa hairpins common
• loops on surface
• diverge rapidly

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Simple Super-2o Motifs

• hairpin ? (?-loop- ?)
• Helix-loop-helix
• Greek key (4 antiparallel ?, wrap)
• ?-?- ? motif (?-alpha helix-parallel ?)

Motifs-Domain Tertiary
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Hairpin ?
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Helix-loop-helixHelix-turn-helix
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Helix-loop-helixHelix-turn-helix
DNA binding EF hand (Ca binding)
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Greek key(4 antiparallel ?, wrap)
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?-?- ? motif(?-alpha helix-parallel ?)
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Protein Structure Viewers

• CnD3 (NCBI)
• .cn3 files (MMDB, NCBI structures)
• CHIME
• WWW compatible, animatable
• RasMol

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Protein Structure databases

• MMDB, NCBI structures
• Cnd3 format
• Protein Data Bank (PDB)
• PDB, Chime, other formats