Protein function (and structure)

DNA binding protein domains
1. many and varied
2. overall basic charge to mediate the interaction with the acidic DNA strand
  1. mostly through interactions with the major groove
3. Several classes of DNA binding proteins containing:
  1. zinc fingers
  2. leucine zipper motifs
    1. dimers of short coiled-coil sequence (the leucine zipper)
      1. As dimers, often form homo- or hetero-dimers increasing the repertoire of available DNA binding proteins.
    2. and a specific DNA recognition helix
    3. Bind DNA like a ‘clothes peg’ on a washing line
  3. basic helix-loop-helix (bHLH)
  4. β-sheet
  5. Some proteins have several motifs in tandem for increased affinity
Modular proteins
1. Made up of several different functional domains
Functional domains
SH2
1. Src Homology 2 domain
2. important phospho-tyrosine binding domain
  1. Binds phosphorylated tyrosine
    1. Often involved in signalling mechanisms
      1. Binding of SH2 domains to their phospho-tyrosine ligands are involved in the formation of signalling complexes
    2. Specific for phospho-tyrosine, but one SH2 domain may interact with p-Tyr in different contexts
      1. Specificity is between the phosphate of the p-Tyr
        some hydrogen bonding also contributes
        mainly ionic interactions between -ve phosphate group and +ve aa’s,
3. Prototypical SH2 domain is from the protein tyrosine kinase Src
  1. Also found in many other signalling and adaptor proteins
SH3
1. Involved in linking structural components
2. Structural roles in maintaining multi-protein complexes
3. Src Homology 3 domain
4. poly-proline binding domain acting as an adaptor to link proteins
  1. Binds proline rich motifs
    1. The minimum consensus sequence for SH3 binding is P-x-x-P,
      1. SH3 domain contains several aromatic residues, these interdigitate between the prolines of the PxxP motif which is stabilised by aromatic stacking
5. Prototypical SH3 domain is from the protein tyrosine kinase Src, but also found in many other signalling and adaptor proteins
PH Domain
1. Binds phospholipids
  1. Phospholipases
    1. Phospholipases have a direct role in lipid signalling
  2. interact with ionic head groups of phospho-lipids anchoring the protein to membrane
2. Role in lipid signalling
  1. and lipid binding
  2. And anchoring proteins to membranes
3. Spectrin
  1. Structural role in maintaining membrane integrity
4. PH Pleckstrin Homology domain
EF Hand
1. octadentate, coordinating through 7 oxygen containing side chains
2. Invariant glycine residue to accommodate the tight turn
3. Binding
  1. Ca2+/Mg2+ has a structural function
  2. binding Ca2+ has a regulatory function
  3. Calcium binding to EF-hands induces structural change e.g. calcium binding to calmodulin
4. back to ppt for diagram
Zinc finger
1. Binds zinc in a structural mode
2. usually structural function in protein-DNA or protein-protein interactions
3. Zn is coordinated tetrahedrally
  1. usually by cysteine or histidine residues
Protein-Protein interactions
1. Require complementary surfaces
2. Bonds may be a combination of
  1. Ionic
  2. Hydrophobic
  3. Electrostatic

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Protein function (and structure)

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	Created by Kristi Brogden over 10 years ago