Wednesday 4 June 2003
Proteins are made of amino acids arranged in a linear chain and joined together by peptide bonds.
Many proteins are the enzymes that catalyze the chemical reactions in metabolism. Other proteins have structural or mechanical functions, such as the proteins that form the cytoskeleton, a system of scaffolding that maintains the cell shape.
Proteins are also important in cell signaling, immune responses, cell adhesion, active transport across membranes, and the cell cycle.
The particular series of amino acids that form a protein is known as that protein’s primary structure. This sequence is determined by the genetic makeup of the individual.
Proteins have several, well-classified, elements of local structure formed by intermolecular attraction, this forms the secondary structure of protein.
They are broadly divided in two, alpha helix and beta sheet, also called beta pleated sheets. Alpha helices are formed of coiling of protein due to attraction between amine group of one amino acid with carboxylic acid group of other. The coil contains about 3.6 amino acids per turn and the alkyl group of amino acid lie outside the plane of coil.
Beta pleated sheets are formed by strong continuous hydrogen bond over the length of protein chain. Bonding may be parallel or antiparallel in nature. Structurally, natural silk is formed of beta pleated sheets. Usually, a protein is formed by action of both these structures in variable ratios. Coiling may also be random.
The overall 3D structure of a protein is termed its tertiary structure. It is formed as result of various forces like hydrogen bonding, disulphide bridges, hydrophobic interactions, hydrophilic interactions, van der Waals force etc.
When two or more different polypeptide chains cluster to form a protein, quaternary structure of protein is formed. Quarternary structure is a unique attribute of polymeric and heteromeric proteins like haemoglobin, which consists of two alpha and two beta peptide chains.
Translation of messenger RNA (mRNA) occurs on the ribosome. Folding of the nascent polypeptide begins, assisted by chaperones.
The polypeptide proceeds to post-translational folding. The new protein is correctly folded into its tertiary structure.
Unfolded or partially folded polypeptides are freed from the aggregates by chaperones and refolded or degraded in the proteasome.
Functional classification (According to Vallee et al., 11237009)
2. modulator proteins
3. receptor proteins
4. transcription factors
5. intracellular matrix component
6. extracellular matrix component
7. transmembrane transporter
9. proteic hormon
11. cell signaling
ligand binding protein or carrier proteins
nucleic-acid binding proteins
transporter proteins (tranport proteins)
signal transducer proteins
unknown or not assigned
According to the localization
- cytoskeletal proteins
vesicle-mediated sorting of proteins
intracellular transport of proteins
protein folding and protein misfolding
protein transport (protein trafficking)
Protein pathology (Proteins citated in humpath.com)
by genic mutation (proteins mutated in human diseases) (In july 2004, 1,484 human genes implicated in human diseases have been listed in Online Mendelian Inheritance in Man - OMIM)
by fixation of an antibody
by fixation of a microbial toxin
by interaction with viral proteins
by chemical inactivation
- gene amplification in tumors
- translocation downstream an activated promoter
- immunoglobulin promoter (IGH, UGK, IGL)
- retroviral insertion near the promoter
- genic therapy by retroviral vector
fusion proteins in tumors
inactivation by mutations
- recessive loss of function mutations
activation by mutations
- resistance to degradation
- creation of new functions
For one protein
splice variant products
assembly into vomplexes
Human Protein Atlas
PROW, Protein Reviews on the Web
InterPro at EMBL-EBI
tigr protein families
PFAM, Protein families database of alignments and HMMs
SCOP, Structural Classification of Proteins at the WEHI, Melbourne, Australia
The Human Protein Reference Database at Johns Hopkins Laboratory
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Chung JJ, Shikano S, Hanyu Y, Li M. Functional diversity of protein C-termini: more than zipcoding? Trends Cell Biol. 2002 Mar;12(3):146-50. PMID: 11859027
Yewdell JW. Not such a dismal science: the economics of protein synthesis, folding, degradation and antigen processing. Trends Cell Biol. 2001 Jul;11(7):294-7. PMID: 11413040
Frand AR, Cuozzo JW, Kaiser CA. Pathways for protein disulphide bond formation. Trends Cell Biol. 2000 May;10(5):203-10. PMID: 10754564