•In proteins, the links of the chain are the amino acids specified by the genetic code.
• Whereas DNA is composed of only four different nucleotides, proteins have a repertoire of 20 common amino acids and, in some special cases, two additional amino acids.
• The only difference between any two amino acids is in their different SIDE CHAINS.
• Each side chain has distinct properties, including
• charge, hydrophobicity, and polarity.
• SIDE CHAINS GIVES EACH PROTEIN ITS CHARACTERISTIC STRUCTURE AND FUNCTION.
• Amino acids, joined together by peptide bonds, form the primary structure of a protein.
• THE AMINO GROUP OF ONE MOLECULE REACTS WITH THE CARBOXYL GROUP OF THE OTHER IN A CONDENSATION REACTION RESULTING IN THE ELIMINATION OF WATER AND THE FORMATION OF A DIPEPTIDE.
• Protein primary structure is divided into two main components,
• the polypeptide backbone that has the same composition in all proteins, and
• THE VARIABLE SIDE CHAIN GROUPS.
Translating The Genetic Code
•A DNA SEQUENCE IS READ IN TRIPLETS USING THE ANTISENSE (NON-CODING) STRAND AS A TEMPLATE THAT DIRECTS THE SYNTHESIS OF RNA VIA COMPLEMENTARY BASE PAIRING.
• The other non-template strand of DNA is called the sense (coding) strand and is the strand of DNA that bears the same sequence as the RNA (except for possessing T instead of U).
• An open reading frame (ORF) in the mRNA indicates the presence of a start codon followed by codons for a series of amino acids and ending with a termination codon.
• There is typically a transcribed but untranslated region of the mRNA (UTR).
•The start codon codes for the amino acid methionine, which is generally cleaved during or after translation to result in the N-terminus of the completed polypeptide.
•The genetic code, deciphered almost 70 years ago, provides the fundamental clues for decoding of genetic information into polypeptides by way of translation.
•In the historical presentation of the genetic code, each “codon box” is composed of four three-letter codes, 64 in all.
•Sixty-one codons are recognized by tRNAs for the incorporation of the 20 common amino acids.
• This observation gave rise to the “wobble hypothesis” proposed by Francis Crick.
• The hypothesis states that the pairing between codon and anticodon at the first two codon positions always follows the usual rule for complementary base pairing, (Watson–Crick base pairing), • but that exceptional “wobbles” (non-Watson–Crick base pairing) can occur at the third position.
• Initially, the genetic code was thought to be universal. Now, it is known that in certain organisms and organelles the meaning of select codons has been changed.
• for example, the specification of serine by CUG in Candida albicans. (in generale, CUG is leucin codon)
• tryptophan by UGA in mitochondria. (in generale UGA is stop codon)
• UAG (stop) pyrrolysine,
• UGA (stop) selenocysteine,
• UAA (stop)
• AUG (start) Methionine.
The 21st And 22nd Genetically Encoded Amino Acids
SELENOCYSTEINE 21st aa.by UGA (in general UGA is a stop codon).
Selenoproteins are essential for mammalian development, as evidenced by the embryonic lethality observed in knockout mice lacking tRNASel.
PYRROLYSINE 22nd aa.
The UAG codon in some instances can trigger incorporation of PYRROLYSINE rather than termination.
Role Of Modified Nucleotides in Decoding
Some modifications selectively restrict anticodon–codon interactions, while others allow tRNAs to respond to multiple codons.
SECONDARY STRUCTURE
Interactions of amino acids with their neighbors gives a protein its secondary structure.
Factors Constructing Secondary Structure of Proteins
a.hydrogen bonds
b.disulfide bridges,
c.van der Waals interactions,
d.hydrophobic contacts, Hydrophobic interactions play a major role in tertiary and quaternary structures of proteins.
e.hydrogen bonds between nonbackbone groups
f.electrostatic interactions.
For example, two R groups having the same charge, either positive or negative, will repel (push) one another. Thus, like (same) charges tend to cause extension, rather than folding, of the chain.
The Three Basic Elements of Protein Secondary Structure Are The
1. α-helix: The right-handed α-helix is the most common structural motif found in proteins Approximately 30% of all residues in globular proteins are found in α-helices.
2. β-pleated sheet: The chains are packed side by side to create a pleated, accordion-like appearance.
3. the unstructured TURNS: Connecting the α-helices and β-pleated sheets elements in protein are “turns.”
Four Levels of Protein Structure
1. The primary protein structure is the sequence of a chain of amino acids.
2. Secondary structures such as the α -helix and the β -pleated sheet are stabilized by hydrogen bonding between nearby amino acids in the chain.
3. Tertiary structure, three-dimensional tertiary structure through noncovalent and covalent interactions. The principal covalent bonds within and between polypeptides are disulfide (S-S) bonds or “bridges” between cysteines. The three main categories of tertiary structure are:
a. Globular The overall shape of most proteins is roughly spherical. lysozyme (an example of globular protein)
b. Fibrous “rod-like” structure collagen α-keratins actin filament cell cytoskeleton silk fibroin
c. membrane proteins transmembrane
cystic fibrosis transmembrane conductance regulator (CFTR)
4. The quaternary protein structure is a protein consisting of more than one amino acid chain. A functional protein can be composed of one or more polypeptides, forming a quaternary structure. The term subunit is generally used to refer to individual polypeptide chains in a complex protein. Quaternary structure can be based on proteins with identical subunits or nonidentical subunits. Hemoglobin
Proteins Contain Multiple Functional Domains
PROTEINS LARGER THAN ABOUT 20 KDA ARE OFTEN FORMED FROM TWO OR MORE DOMAINS THAT ARE GENERALLY ASSOCIATED WITH SPECIFIC FUNCTIONS.
Common Structural– Functional Motifs
a finger-shaped motif called a zinc finger that is involved in DNA binding,
leucine zipper family of DNA-binding proteins a coiled-coil region.
Prediction Of Protein Structure
1. computer algorithms
2. X-ray crystallography
3. nuclear magnetic resonance (NMR)
4. robotic systems
5. X-ray diffraction
Protein Function
Structures
Cytoskeleton
Hormones
transport oxygen
mediate the activities of genes
from replication to transcription to translation
enzymes
Great importance of enzymes for the discussion of protein structure and function are; the roles of post-translational modifications and allosteric regulation in controlling protein activity.
• Complexes that form between lipids and proteins are called lipoproteins,
• proteins with a carbohydrate moiety attached are called glycoproteins,
• Protein complexes with metal ions are termed metalloproteins, and so on.
The Post-Translational Modifications Can Have Both Structural and Regulatory Functions
• methylation,
• acetylation,
• ubiquitinylation,
• sumoylation. (Small Ubiquitin-like Modifier)
• phosphorylation (most common)
Many steps in gene expression and cell signaling pathways involve posttranslational modification of proteins by phosphorylation
Levels Of Regulation of Protein Activity
• transcription,
• RNA processing,
• translation,
• post-translational modifications
SINGLE PROTEINS CAN CATALYZE BIOCHEMICAL REACTIONS, BUT HIGHER CELLULAR FUNCTIONS DEPEND ON CAREFULLY ORCHESTRATED PROTEIN INTERACTION NETWORKS.
Protein Folding and Misfolding Protein Katlanması Ve Yanlış Katlanması
•In some cases, protein folding is initiated before the completion of protein synthesis on ribosomes. •Bazı durumlarda ribozomlarda protein sentezi tamamlanmadan protein katlanması başlar.
•Other proteins undergo a major part of their folding after release from the ribosome in either the cytoplasm or in specific compartments such as mitochondria or the endoplasmic reticulum. •Diğer proteinler, ribozomdan salındıktan sonra katlanmalarının büyük bir kısmını sitoplazmada veya mitokondri veya endoplazmik retikulum gibi spesifik bölümlerde geçirirler.
•Most proteins require other proteins called “MOLECULAR CHAPERONES” to fold properly in vivo. • Çoğu proteinin in vivo olarak düzgün şekilde katlanabilmesi için “MOLEKÜLER ŞAPERONLAR” adı verilen diğer proteinlere ihtiyaç vardır.
•Incorrectly folded proteins are generally targeted for degradation. •Yanlış katlanmış proteinler genellikle bozunma için hedeflenir.
• The accumulation of misfolded proteins is associated with several human diseases. • Yanlış katlanmış proteinlerin birikmesi bir dizi insan hastalığıyla ilişkilidir.
Molecular Chaperones Moleküler Şaperonlar
•MOLECULAR CHAPERONES INCLUDE HEAT SHOCK PROTEINS, SUCH AS HSP40, HSP70, AND HSP90, WHICH PROMOTE PROTEIN FOLDING AND AID IN THE DESTRUCTION OF MISFOLDED PROTEINS. •MOLEKÜLER ŞAPERONLAR, PROTEİN KATLANMASINI DESTEKLEYEN VE YANLIŞ KATLANMIŞ PROTEİNLERİN YOK EDİLMESİNE YARDIMCI OLAN HSP40, HSP70 VE HSP90 GİBİ ISI ŞOKU PROTEİNLERİNİ İÇERİR.
•The designation of these as heat shock proteins reflects the fact that their concentrations are substantially increased during cellular stress. •Bunların ısı şoku proteinleri olarak adlandırılması, hücresel stres sırasında konsantrasyonlarının önemli ölçüde arttığı gerçeğini yansıtmaktadır.
Protein Conformational Diseases
a. Alzheimer’s disease
b. Parkinson’s disease
c. Huntington’s disease
d. type II diabetes
e. mad cow disease in domesticated animals
f. Kuru and Creutzfeld–Jakob disease in humans