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Protein Structure and Function

Protein Structure and Function. 1 , 2 , 3 , 4  Structure Viewing, interpreting structure Protein Characterization. BIO520 Bioinformatics Jim Lund. ~100 to >10,000 aa Soluble Integral membrane proteins Membrane-associated Single domain, multiple domains

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Protein Structure and Function

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  1. Protein Structure and Function 1, 2 , 3 , 4  Structure Viewing, interpreting structure Protein Characterization BIO520 Bioinformatics Jim Lund

  2. ~100 to >10,000 aa Soluble Integral membrane proteins Membrane-associated Single domain, multiple domains singular, multimeric, large complex Protein variety DIVERSE

  3. 1 structure aa sequence 2  structure regular local folding 3  structure packing and overall folding 4  structure polypeptide:polypeptide complexes Protein Structure

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

  5. Dogma Sequence=Structure Similar Sequence Similar Function Kinetics vs Thermodynamics Chaperones

  6. Restricted, but considerable rotation Different residuesdifferent , Regular ,  helix  sheet , angles

  7. Experimental , angles Hovmöller et al., 2002. Conformations of amino acids in proteins

  8. An example Ramachandran plot Ideal a kinase

  9. H-bonding orientation (dielectric) Hydrophobic effect nonpolar to core Ionic interaction + to -, (dielectric) Dipole effects  helix, N to C (+ to -) Forces holding proteins together

  10. 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 -helix

  11. Parallel or antiparallel N-to-C Mixed -sheets are rare: only ~20% of -sheets are mixed parallel/anti-parallel. “pleated” and “twisted” aa preferences -sheet

  12. Length, conformation variable 2 aa hairpins common loops on surface diverge rapidly -turn, loops

  13. hairpin  (-loop- ) Helix-loop-helix Greek key (4 antiparallel , wrap) --  motif (-alpha helix-parallel ) Simple Super-2o Motifs Motifs-Domain Tertiary

  14. Hairpin 

  15. Helix-loop-helixHelix-turn-helix

  16. Helix-loop-helixHelix-turn-helix DNA binding EF hand (Ca++ binding)

  17. Greek key(4 antiparallel , wrap)

  18. --  motif(-alpha helix-parallel )

  19. Cn3D (NCBI) .cn3 files (MMDB, NCBI structures) RasMol ProteinExplorer CHIME WWW compatible, animatable Jmol WWW compatible, animatable Protein Structure Viewers

  20. Protein Viewing conventions

  21. MMDB, NCBI structures Cn3D format (ASN1) Protein Data Bank (PDB) PDB, Chime, other formats (http://www.pdb.org) Protein Structure databases

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