A protein is a type of molecule that performs a specific job in living things, with each different protein carrying out its own job. You can think of proteins as **molecular machines or tools** that carry out a specific function. These functions can vary a lot from: - Providing structural support to a cell (like scaffolding) - Transporting things (like haemoglobin in the blood carries oxygen) - Speeding up chemical reactions - Acting as sensors or messengers What makes proteins unique is that each one has a **precise 3D shape** that determines what it can do and changes to this shape can effect its function. I will also clarify, even though one type of protein has a specific shape and specific job, it doesnt mean all cells have all proteins and cells may make lots of one type of protein and not many of another. Furthermore, some proteins might look completely different but may carry out the same job as another. Proteins are **polymers**, meaning they're long chains made up of repeating building blocks called **monomers**. In the case of proteins, these monomers are **amino acids**. When amino acids link together, they form a **polypeptide chain**, which then folds into a functional protein. When referring to amino acids **within** a protein chain (rather than as free molecules), they’re usually called **residues**. there are steps to protein structure ### Primary structure Primary structure is the order of the amino acids within the chain. It is the foundation for the protein, different amino acids have different properties and allow and mediate different interactions within the protein itself (eg [[disulphide bond]]), other proteins or molecules. Each amino acid is linked to the next amino acid through peptide bonds created during its synthesis:  # Amino acids Amino acids share a common core structure but differ in their **side chains**, which give them specific functions. Each amino acid has a **chiral center** which is an important property. Its a bit like your left and right hands, two mirror-image versions (called **L** and **D** forms) can exist. Even though they contain the same atoms, and may look very very similar, they are **not interchangeable**. In nature, proteins almost exclusively use the **L-form** of amino acids. > **Glycine** > Non polar [[Aliphatic]] amino acid. its R group is 1 H > - Favours coils and disrupts Helixes due to its minimal R group and flexibility. > - Prefers to substitute with small amino acids > >**Alanine** > Non Polar [[Aliphatic]] amino acid with a CH3 R group > - Second most prevalent amino acid > - Hydrophobic and packs well in protein structures. Non reactive > - Prefers to substitute with small amino acids > > **Proline** > Non polar [[Aliphatic]] Amino acid with a ring shaped R group comprised of CH2-CH2-CH2 bonded to both the amine group and to the central alpha carbon. >- Has a rigid inflexible structure due to its ring and leads to rigid turns bordering α-helices and β-sheets. Usually found on the protein surface due to its turn-abilty. > - It moves through the ribosome slowly. > - It doesn’t substitute well with other amino acids due to its unique structure but favours small residues > > **Valine** > Non polar [[Aliphatic]] amino acid with an R group of CH with two branching CH2 groups > - Very non-reactive but as it hydrophobic can be involved in recognition of hydrophobic ligands. > - Prefers substitution with amino acids of the same type > > **Leucine** > Non polar [[Aliphatic]] amino acid with a C4H9 branched R group >- Prefers to be buried in the hydrophobic core and some preference for being in helices and sheets. >- Very non-reactive but as it hydrophobic can be involved in recognition of hydrophobic ligands. >- Prefers substitution with amino acids of the same type > > **Isoleucine** > non polar [[Aliphatic]] amino acid with C4H9 branched R group >- Prefers to be buried in the hydrophobic core. Due to bulkiness near the backbone it is more rigid >- Very non-reactive but as it hydrophobic can be involved in recognition of hydrophobic ligands. >- Prefers substitution with amino acids of the same type > > **Methionine** > non polar [[Aliphatic]] amino acid with a CH2CH2SCH3 R group > - Prefers substitutions with hydrophobic amino acids > - Likes to be buried in the hydrophobic core. > - Sulphur can bind metal ions but is not very reactive- ultimately non-reactive but as it hydrophobic can be involved in recognition of hydrophobic ligands. > >These 7 amino acids have similar properties and are hydrophobic meaning they are poorly soluble in water (tendency to avoid/repel water) they are often involved in stabilisation and cluster together within proteins to avoid contact with waters. > **serine** > polar non-charged with R group of CH2OH > - Prefers substitutions with polar amino acids in particular threonine > - relatively common within tight turns on the protein surface > - found in the classical Asp-His-Ser catalytic triad found in many hydrolases > > **threonine** > polar non charged with branched R group of CHCH3OH > - Prefers substitutions with polar amino acids in particular Serine > - Bulk is close to the back the back bone preventing rotation > - Found in functional centres and active sites due to being fairly reactive > > **Cysteine** > polar non charged with R group of CH2SH is a weak acid > - No preference for substitutions but prefers small amino acids when intracellular. > - In extracellular proteins/domains can form di-sulphide bonds but this unlikely in the reducing intracellular environment. > - Sulfhydryl can bind metal ions. > - very common in protein active and binding sites >can form a disulphide bond with itself forming cystine- this is very functionally relevant and plays a role in formation of proteins covalently linking pars of the protein or proteins together. this formation is very hydrophobic, losing its polarity. > > **Asparagine** > polar Non-charged with branched R group of CH2CNH2O (an Amide) > - Prefers substitutions with polar amino acids notably aspartate > - Likes to be surface exposed > - Often found in binding sites and is part of the Asn-His-Cys catalytic triad > > **Glutamine** > polar non charged with R group of CH2CH2CNH2O (an amide) > - Prefers substitutions with polar amino acids notable glutamate > - Likes to be surface exposed > - Often found in binding sites. > >these amino acids have R groups that are more soluble in water and can form Hydrogen bonds. > **glutamate** > negatively charged with an R group of CH2CH2COO- > - Prefers substitutions with Aspartate but will tolerate substitutions with polar amino acids namely Glutamine. > - Likes to have the OH- group on the outside of proteins and will form salt-bridges > - Often found in binding sites and can form multiple hydrogen bonds, slightly more flexible than aspartate > > **Aspartate** > negatively charged with and R group of CH2COO- > - Prefers substitutions with glutamate but will tolerate substitutions with polar amino acids namely asparagine. > - Likes to have the OH- group on the outside of proteins and will form salt-bridges > - Often found in binding sites and can form multiple hydrogen bonds, slightly more rigid than glutamate > > these amino acids are some of the most hydrophilic > **Lysine** > positively charged with an R group of CH2CH2CH2CH2NH3+ > - Prefers substitutions with arginine but will tolerate substitutions with polar amino acids. > - Likes to have the NH3+ group on the outside of proteins and will form salt-bridges > - Often found in binding sites and can form multiple hydrogen bonds > > **Arginine** > positively charged with an R group of CH2CH2CH2NHCNH2(NH2+) > - Prefers substitutions with Lysine but will tolerate substitutions with polar amino acids. > - Likes to have the NH3+ group on the outside of proteins and will form salt-bridges > - Often found in binding sites and can form multiple hydrogen bonds > > **Histidine** > positively charged with a ring like R group oc C=CHNCHNH > - Doesn’t substitute well and is easily protonated and deprotonated > - Ideal residue for functional centers and active sites. In metal binding sites it is not uncommon to see it substituted with Cysteine >the only common amino acid with an ionisable (can donate or accept electrons) side group, it often is involved in enzymatic active sites due to this property > >These amino acids are also very hydrophilic > **Phenylalanine** > an amino acid with an aromatic R group of CH2(C6H5) > - Prefers substitutions with hydrophobic, aromatic amino acids especially Tyrosine > - Likes to be buried in the hydrophobic core and get involved with stacking interactions. > - Can interact with non-protein ligands that also contain an aromatic group > > **Tyrosine** > an amino acid with an aromatic R group of CH2(C6H4)OH > - Prefers substitutions with hydrophobic, aromatic amino acids particularly phenylalanine > - Likes to be buried in the hydrophobic core and get involved with stacking interactions. > - More likely to be involved in non protein interactions due to it OH group > - Offers up some fluorescence due to its aromatic R group. > the OH group can contribute to the formation of H-bonds > **Tryptophan** > an amino acid with an aromatic R group of C7H4(NHCH) > - Likes to be buried in the hydrophobic core and get involved with stacking interactions. > - Can interact with non-protein ligands that also contain an aromatic group > - Most of the intrinsic fluorescence emissions of a folded protein are due to excitation of tryptophan residues > > these amino acids are relatively non polar and contribute to the hydrophobicity. # Secondary structure The secondary structure is the spatial conformation of the polypeptide chain when only the Amino hydrogen and Carboxyl oxygen hydrogen bonds are considered. It is not a real structure it exists as a sort of pseudo intermediate structure before the R-group interactions are considered. > # **β**-pleated sheet > The β-pleated sheet is a common structural motif found in proteins. They are formed with lateral β-strands (near linear peptide chains) that then connect to each other laterally via Hydrogen bonds (N-H//C=O) forming a sheet like structure. > the sheets can either be parallel or anti-parallel > ![[beta sheet 1.jpg|250]]