Different levels of protein structure

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Dr. Sanjeeva Srivastava Proteins and its function Amino acids: building blocks Different levels of protein structure Primary, Secondary, Tertiary, Quaternary 2 Proteomics ourse PTEL 1

Derived from Greek Proteios Linear polymers built of monomers (amino acids) Most versatile macromolecules in living systems Play key structural and functional roles Proteomics ourse PTEL Promoter T A T A DA Sequence Message A G T A G T Q Y R Protein Sequence & Regula5on Protein Structure Protein/ Enzyme Structure 4 Proteomics ourse PTEL 2

ff n SIGALLIG REGULATI TRASPRT Protein Functions STRUTURE MVEMET ATALYSIS Α Β 5 Proteomics ourse PTEL 6 Proteomics ourse PTEL

2 2 2 2 Glycine 2 Alanine 2 Proline Valine Leucine Isoleucine Methionine 7 Proteomics ourse PTEL 2 2 S 2 Serine 2 2 Asparagine Threonine 2 2 2 Glutamine 2 S ysteine 8 Proteomics ourse PTEL 4

2 2 2 2 2 2 2 2 2 2 Lysine Arginine is5dine 9 Proteomics ourse PTEL 2 2 2 Aspartate Glutamate 10 Proteomics ourse PTEL 5

2 2 2 Phenylalanine Tyrosine Tryptophan ydrophobic character ydrophobic ydrophilic 11 Proteomics ourse PTEL 10,000 Extinction coefficient 8,000 6,000 4,000 2,000 0 220 240 260 280 00 20 Wavelength (nm) 12 Proteomics ourse PTEL 6

LIsomer DIsomer R R α α 1 Proteomics ourse PTEL R α 14 Proteomics ourse PTEL 7

R R R Zwitterionic Form Both groups Protonated Both groups Protonated 0 2 4 6 8 10 12 14 15 Proteomics ourse PTEL R1 R2 R1 R2 20 16 Proteomics ourse PTEL 8

R1 R R2 R4 Backbone 17 Proteomics ourse PTEL α α 18 Proteomics ourse PTEL 9

ˉ 19 Proteomics ourse PTEL Trans Trans α α is α α 20 Proteomics ourse PTEL 10

is α α α α Trans 21 Proteomics ourse PTEL 22 Proteomics ourse PTEL 11

Glycine Alanine 4 2 ondensa5on Valine Free amino acids Lysine Primary Structure 2 Proteomics ourse PTEL 2 2 2 _ 24 Proteomics ourse PTEL 12

Essential for elucidation of its mechanism of action Determines -D structure of proteins Amino acid alteration can produce abnormality Sequence tells us an evolutionary history of protein 25 Proteomics ourse PTEL R2 α α Ψ α R1 R 26 Proteomics ourse PTEL 1

Phi Ψ 180 150 120 90 60 0 0 0 60 90 120 150 180 180 150 120 90 60 0 0 0 60 90 120 150 180 Psi = 90, Ψ = - 90 27 Proteomics ourse PTEL 28 Proteomics ourse PTEL 14

Ball and stick model Ribbon diagram 29 Proteomics ourse PTEL Ri Ri2 Ri4 Ri1 Ri Ri5 Residue i () i 4 () 0 Proteomics ourse PTEL 15

α-keratin Two α helices wrap to form a stable structure ollagen It contains helical polypeptide chain 1 Proteomics ourse PTEL β sheets: another common, periodic structural motif Fully extended structure Parallel Anti-parallel 2 Proteomics ourse PTEL 16

More elaborate structures loops or omega turns Loops are rigid, no periodic structures Turns and loops on surfaces Participate in protein and other molecule interactions Proteomics ourse PTEL α helix Polypeptide chain tightly coiled Rod like structure Axial distance 1.5 A -bond between and groups in same polypeptide chains Examples Ferritin, keratin, collagen β sheets Polypeptide chain fully extended Sheet like structure Axial distance.5 A -bond between and groups in different polypeptide chains Fatty acid binding protein 4 Proteomics ourse PTEL 17

5 Proteomics ourse PTEL Three dimensional compactly folded structure of proteins verall organization of secondary structural elements in -D space 6 Proteomics ourse PTEL 18

7 Proteomics ourse PTEL Final level of protein structure Spatial arrangement of subunits and their interactions Polypeptide chains assemble to form multisubunit structure 8 Proteomics ourse PTEL 19

α- subunits α β β α Individual polypeptide chains β- subunits Quaternary structure (emoglobin) 9 Proteomics ourse PTEL DA Genetic blueprint RA molecular photocopy Proteins Building blocks 40 Proteomics ourse PTEL 20

Proteins and its function Amino acids: building blocks Different levels of protein structure Primary, Secondary, Tertiary, Quaternary Myoglobin and emoglobin Proteins and diseases 41 Proteomics ourse PTEL Berg J., Tmyoczko J. & Stryer L., Biochemitry fifth ed., W.. Freeman & company, 2002. ISB: 0716746840. elson D. & ox M.,Lehninger, Principles of Biochemistry fourth ed., W.. Freeman and company, 2004.. ISB: 02022699X. Voet D. & Voet J., Biochemistry fourth ed., Wiley, 2000. ISB: 047158651X. Proteomics ourse PTEL 21