E2: Intro to proteins Flashcards
binding is characterised by what two properties?
affinity and specificity
how do receptors work?
sense and transmit singals via a cascade signal transduction pathways
what do antibodies do?
part of our immune defenses and recognize and help destroy foreign bodies that enter
our bodies
what is a glycoprotein
Protein + carbohydrate
what is a lipoprotein
Protein + lipid
how many standard amino acids are there which are common to all species?
20
Describe the structure of an amino acid
central carbon atom (C) with 4 groups attached;
* Primary amino group (- NH2 )
* Carboxyl group ( - COOH)
* Hydrogen atom
* Variable ‘R’ group or side chain (one exception to this structure is proline; R group bonds with Ca & amino
group)
what is chirality?
2 non-superimposable mirror images; enantiomers or stereoisomers. Distinguished by optical rotation of plane polarized light
all amino acids except which are enantiomers?
glycine (R group is hydrogen so it is symmetrical)
Describe D-amino acids, Dextrorotatory (D; right)
rare in nature, but seen in bacterial cell wall and some antibiotics
Describe L-amino acids, laevorotatory (L; left)
predominant form found in proteins
what contributes the the properties and functions of proteins
R side chains vary in size, shape, charge, H-bonding capacity, hydrophobicity and chemical reactivity
In terms of pH, what is the usual form amino acids exist in solution?
(neutral) zwitterion, depending on the pH, there are two other forms, an anion and a cation: anion at high pH and cation at low pH (look at one note for diagram)
As the pH decreases a H+ ion will be added to the carboxylate; as the pH increases the H+ will be removed from the NH3+ and this also applies to the R groups
which amino acids have hydrophobic interactions
non-polar, aliphatic amino acids. The aromatic side chains are hydrophobic
which amino acids undergo hydrophilic interactions
-polar, uncharged amino acids
-positive or negative side chains tend to be hydrophilic
what is the primary sequence?
linear sequence of amino acids to form a polypeptide
Describe a peptide bond
covalent; amino group of one amino acid and carboxyl of another
peptide bond is planar meaning…
restricting movement of the backbone of proteins
Describe torsion angle in proteins
Torsion angle is the angle between groups on either side of a rotatable chemical bond; in proteins;
* The C-N (phi) bond is called phi
* The C-C (psi) bond is called psi
These rotations drive protein folding and how amino acids interact with each other
Describe secondary structure of proteins
the localized organization of parts of a polypeptide chain (e.g., helix or sheet) Super-secondary structure; specific combination of several secondary structure elements
Simple arrangement of structures that occur in more than one protein are called motifs or folds and can help ascertain function e.g., a binding site
Describe tertiary structure
the overall, three-dimensional (3-D) arrangement of the polypeptide chain Also includes details of binding of any prosthetic groups
Describe the quaternary structure
the organisation of two or more polypeptides chains into a multi-subunit complex
Describe alpha helix secondary structure
-formed/stabilized by H-bonding between carbonyl of first and amino group of fifth amino acid in helix, then second with sixth etc
-R side chains face outwards
-Cylindrical structure with R groups all positioned on outside of helix
-Proline has distinct hydrogen bond pattern and cannot contribute to a-helix structure; often found at end
of a-helix ‘forcing’ directional change in polypeptide
Describe beta ‘pleated’ sheet
-H-bonds between alternating residues on beta strands: occurs between the amino and carbonyl groups of alternating residues
-R groups face up and down out of the plane of the sheet
-Can run in anti-parallel and parallel arrangements
-multiple beta sheets provide strength and rigidity
Describe connecting loops (coils) secondary structure
Not repetitive, containing fewer backbone hydrogen bonds. Sections that connect the regular structures of helices and sheets
Describe the tertiary structure
-determined by amino acid sequence and R- group properties
-Stabilised by non-covalent: hydrogen bonds, hydrophobic interactions, ionic interactions and covalent disulfide bridges between cysteine residues (if present)
-Tertiary structure is also driven by hydrogen bonding interactions of the hydrophilic side chains and the backbone with water
what are domains
distinct regions with specific geometry/structure performing specific function e.g., enzyme binding a substrate
Describe quaternary structure
- The association of two or more polypeptide chains into a multi- subunit structure
- Homomeric (identical polypeptide chains) heteromeric (different chains)
- Stabilized by hydrogen bonds and van der Waals forces`
- May also include prosthetic groups
What is protein folding determined by?
- Folding is determined by their amino acid composition, which involves their physico-chemistry and thermodynamics
- Secondary structures often form spontaneously, but the full 3D tertiary structure does not, and accessory proteins are required to assist the process of folding
Describe the disulphide bond
-covalent bond between cysteine amino acids
* Facilitates intra and inter-molecule bonding
* Function to stabilize the overall 3D structure
* Formed under oxidizing conditions in the ER and are mainly found in secreted proteins and proteins of the extra-cellular matrix
what are super-secondary structures (sometimes called structural motifs)?
combinations of 2 or more secondary structure elements
what are the two main classes of domain?
functional and structural
-domains represent larger recognisable regions of proteins
Describe functional domains
mediate a particular activity of the protein, for instance the ability to bind to DNA or an enzymatic activity
Describe structural domains
a region of around 40 or more amino acids that form a stable secondary and tertiary structure. Often the domain can fold into this structure independently of the rest of the protein
what are globular proteins
high water solubility, compactly folded. Includes most enzymes and transporters like haemoglobin
What are fibrous proteins?
elongated proteins, with low water solubility, large amounts of regular secondary structure, that often form stiff multimeric fibres e.g., Collagen, elastin, keratin
What is collagen
triple, left-hand helix structure with each polypeptide having a regular repeating amino acid sequence; Many of these triple helix molecules pack together to form fibres
why is protein structure important for drug development?
we can model, predict and demonstrate specific binding/interactions of many drug molecules and is a key aspect of understanding how they work (and new ones
discovered/developed)
how are most proteins degraded?
Proteins with well-structured domains are difficult to access for proteases therefore they are degraded by the ubiquitin-proteasome pathway
what occurs in the ubiquitin-proteasome pathway
-Multiple copies of the small protein ubiquitin are coupled to a lysine residue in the protein to be degraded by specific ligases: a process called polyubiquitination
* A large protein complex called the proteasome recognises the polyubiquitin chain, unwinds the secondary structure of the ubiquitinated protein and hydrolyzes it into small peptides
Describe biomarkers to detect tissue damage/disease
- Myocardial infarction (heart attack) damages the myocardium
- Can result in release of cardiac muscle proteins into circulation, which can be detected and gauge severity of damage
e.g Creatinine kinase (involved in ATP synthesis) and Troponin (sarcomere protein, interacting with actin)
Describe proline amino acid
R-group bonds back onto the amino group
Describe cysteine amino acid group
can form disulfide bonds between the side chains
The protein backbone can only rotate on what two bonds with the alpha carbon?
the φ (psi) angle rotation around the bond with the nitrogen and the ψ (phi) angle rotation around the bond with the carbonyl carbon. Steric hindrance prevents some combinations of these angles also from occurring
proteins can be divided in what classes?
-Structural proteins
-Scaffold proteins
-Enzymes
-Membrane transport proteins
-Regulatory and signalling proteins
-Motor proteins
Where is the form and function of a protein derived from?
protein function is derived from the three-dimensional structure and this structure is determined primarily by the non-covalent interactions between the amino acids in the linear amino acid chain. It is therefore specified by the amino acid sequence.
What is the N terminus and C terminus
The free amino terminal end of the peptide chain is called the N terminus and the free carboxyl end the C terminus. amino acid sequences are numbered from N to C terminus
what is the secondary structure of a protein
regular arrangements of the backbone of the polypeptide chain, which are stabilized by the formation of hydrogen bonds between the amino and carbonyl groups in the backbone of the protein
what is protein stability and the 3D conformation maintained by?
a range of non covalent interactions (electrostatic forces, hydrogen bonds and hydrophobic forces) and covalent interactions (peptide and di-sulphide bonds). Some proteins need prosthetic group that binds tightly to protein and participates in its function.
what are the three main structural classes of proteins
1) Globular
2) Fibrous
3) Membrane- transmembrane proteins (integral) and lipid-anchored proteins (peripheral)
what structural motifs or folds?
some short combinations of secondary structures. They often mediate a similar function, for instance binding
Describe the structure of myoglobin?
single polypeptide chain that folds to give a tertiary structure that comprises 8 alpha helices, which are labeled A-H in 3D models. Also contains haem group.
Describe the haem group?
protoporphyrin IX ring structure with a single iron atom (Fe2+). Iron atom bonds with 4 nitrogen atoms and forms two additional bonds- one with a histidine amino acid along the F helix; the other bond it makes is with oxygen
