1 - Protein classification, Fct & Folding Flashcards
Classification
Shape
- Globular proteins: protein axis correlation is lower than 1:30
- Fibrillar proteins: > than 1:30
- Collagen: triple helical structure of repetitions of glycine-proline-hydroxyproline
- Keratins - type I + II (a-coil-coil motif stabilised by hydrophobic) - high cysteine
Content
- Glycoproteins, Lipoprotein, Nucleoproteins, Metaloprotein, Hemoproteins
Functional Roles of Proteins in Humans
- Enzymes: catalyse chemical reactions
- Transport: in membranes or blood (Hb, tranferin…)
- Hormones: insulin, glucagon, ACTH, GH, FSH, LH, PLT
- Protection: IG, interferon, fibrin
- Regulation of gene transcription and translation
- Contraction -
- Receptors
- Structural - collagen, elastin, keratin
Protein Folding
Native structure = physiologically active conformation of a protein (related to the Anfinsen’s law - 2o, 3o, 4o structures determined by 1o. The folding proceeds in a manner to reach the lowest free energy and there is a hierarchy:
- Formation of secondary structures with 8-16AA
- Formation of domains
- Association of domains to form the molten globule (state between the native and the fully unfolded states of a protein)
- The molten globule is converted into tertiary structures
- The 3o structures of several form the subunits that associate and form quaternary structures
V rapid in cells but hours to refold denatured in lab - accel by accesory
Chaperones mediate the correct assembly of proteins but are not part of the final functional structures. They use ATP and the most important ones are:
- HSP 70 (ribosomes) - heat shocks protein
- HSP 47 (collagen)
- Nucleoplasmin (nucleosome formation)
Enzymes that speed up folding:
- Protein disulphide isomerase
- Prolyl cis-trans isomerase
Under the influence of low pH or high temperatures, the native conformation is destroyed and a denatured structure without function occurs
Protein disulfide isomerase - S-s bond for under ox conditions w/i and between pp to stabilize 3o and 4o
Prolyl-cis-trans-isomerase - catalyses isomerisation
Post translational modifications
Modified to ensure appropriate properties:
- Acetylation - cell reg e.g. histones epigentic reg
- Hydroxylation: prolines and lysines are hydroxilated in collagen
- Phosphorylation: catalysed by kinases with the expense of ATP. It is usually a reversible process
- Glycosylation
- Carboxylation - carboxylases contain vit K
- Methylation: important in gene expression
- Ribosylation - usually in prescense of NAD
Biologically Active Peptides
- Anserine: maintains pH in muscles =b-alanyl-methylhistidine
- Glutathione: transport of AA, redox w/ RBC (y - glu-cys-gly)
- Vasopressin - ^bp as ^ reabsorption of water. Cyclic nanopeptide w/ intrinsic disulf B (arg-ADH/lys-ADH forms)
- Oxytocin - cyclic peptides (differ from ADH by 1/2 AA residues) - Uterus contraction and milk ejection
- Enkephalins: analgesic neuropeptides serving as neuromodulators and neurotransmitters)
- Met-enk/Leu-enk {tyr-gly-gly-phe-x]
- Endorphins -neuropeptides of CNS
- B-lipotropin - pituitary hormone - releas FA from adipose tissue
- releasing factors - control release of pituitary hormones e.g. TRH
