Protein Structure and Function 1 , 2 , 3 , 4 Structure Viewing, interpreting structure Protein Characterization BIO520 BioinformaticsJim Lund
Protein variety ~100 to >10,000 aa Soluble Integral membrane proteins Membrane-associated Single domain, multiple domains singular, multimeric, large complex
Protein Structure 1 structure –aa sequence 2 structure –regular local folding 3 structure –packing and overall folding 4 structure –polypeptide:polypeptide complexes
Modifications Proteolysis/processing Residues Modified –cysteine disulfides –phosphorylation –methylation Heteroatoms –Metal ions, heme, cofactors….
Dogma Sequence=Structure
, angles Restricted, but considerable rotation Different residues different , Regular , – helix – sheet
Experimental , angles Hovmöller et al., Conformations of amino acids in proteins
An example Ramachandran plot Ideala kinase
Forces holding proteins together H-bonding –orientation (dielectric) Hydrophobic effect –nonpolar to core Ionic interaction –+ to -, (dielectric) Dipole effects – helix, N to C (+ to -)
-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
-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
-turn, loops Length, conformation variable –2 aa hairpins common loops on surface diverge rapidly
Simple Super-2 o Motifs hairpin ( -loop- ) Helix-loop-helix Greek key (4 antiparallel , wrap) - - motif ( -alpha helix-parallel )
Hairpin
Helix-loop-helix Helix-turn-helix
DNA binding EF hand (Ca++ binding)
Greek key (4 antiparallel , wrap)
- - motif ( -alpha helix-parallel )
Protein Structure Viewers Cn3D (NCBI) –.cn3 files (MMDB, NCBI structures) RasMol –ProteinExplorer –CHIME WWW compatible, animatable –Jmol WWW compatible, animatable
Protein Viewing conventions
Protein Structure databases MMDB, NCBI structures –Cn3D format (ASN1) Protein Data Bank (PDB) –PDB, Chime, other formats –(