A protein's biological specificity is determined by its structure and chemistry.
Proteins can be separated into two broad classes based on whether they are present in all or specific cells: housekeeping proteins present in nearly every cell which maintain cell structure and function; and tissue-specific specialty proteins present in only some cells and with unique cell-specific functions.
If a specialty protein is mutated, a disease phenotype will usually be limited to tissues inhabited by relevant cells (a notable exception is phenylketonuria). If a housekeeping protein is mutated, oftentimes only tissues where that protein has a heightened/unique role will be affected.
Also, mutations in proteins essential for every tissue (such as DNA Polymerase) are rarely viable at all.
Hydropathy is the primary factor in protein structure: neutral and non-polar amino acids are hydrophobic and tend to be tucked away inside the protein structure, rather than exposed to the aqueous environment.
Neutral and polar amino acids form primarily hydrogen bonds. Acidic and basic amino acids form primarily ionic bonds. Also, the shape of the amino acid plays a factor: is it bulky, like the cumbersome aromatic amino acids? Is it flexible, with freely rotating single bonds?
Structure – similar sequences form similar structures.
Function – motifs (sequence patterns) can indicate particular functions
Location – signal sequences (at the protein’s N-terminus) direct proteins to specific locations in the cell, or to be excreted
Modification – signal sequences or motifs can indicate sites for modification
Evolution – differences in related sequences reflect evolutionary distance
Dysfunction – changes in sequence can lead to disease
Primary protein structure
Linear chain of amino acids.
Secondary protein structure
Tertiary protein structure
The helix forms more readily than other conformations because it makes optimal use of hydrogen bonds. Alanine is most likely to form alpha helices, while proline and glycine are least likely to. Methionine, alanine, leucine, uncharged glutamate, and lysine ("MALEK" in the amino-acid 1-letter codes) all have especially high helix-forming propensities, whereas proline and glycine have poor helix-forming propensities. Proline either breaks or kinks a helix, both because it cannot donate an amide hydrogen bond (having no amide hydrogen), and also because its sidechain interferes sterically with the backbone of the preceding turn - inside a helix, this forces a bend of about 30° in the helix axis. However, proline is often seen as the first residue of a helix, presumably due to its structural rigidity. At the other extreme, glycine also tends to disrupt helices because its high conformational flexibility makes it entropically expensive to adopt the relatively constrained α-helical structure.
Tend to stack, so small groups like glycine and alanine tend to be found in sheets. Large aromatic residues (Tyr, Phe and Trp) and β-branched amino acids (Thr, Val, Ile) are favored to be found in β strands in the middle of β sheets. Interestingly, different types of residues (such as Pro) are likely to be found in the edge strands in β sheets, presumably to avoid the "edge-to-edge" association between proteins that might lead to aggregation and amyloid formation. It is also suggested that the dipole moments in parallel β-sheets, whose direction is from C-terminal (partially negative) to N-terminal (partially positive) may influence the propensity of certain residues (like Lys and Arg) for the caps of this structure
Quaternary protein structure
Interaction of multiple subunits (disulfide bridges, hydrophobic side chains, ionic bonds of charged side chains (salt bridge).
Functions fall into the following groups:
Function is altered/impaired by the following chemical conditions:
pH (acid or basic)
Chemicals (polar & non-polar)