1. Marlou Snelleman 2012 Proteins and amino acids

2. Overview Proteins Primary structure Secondary structure Tertiary structure Quaternary structure Amino acids Building blocks of proteins Properties

3. Proteins Primary structure The sequence Secondary structure α-helices β-strands Turns Loops Tertiary structure Interactions between the secondary structure elements to form the structured protein Quaternary structure Dimers or multimers of proteins

4. Primary structure Proteins are polymers The monomers (residues) are amino acids The sequence: is the order of the amino acids in the protein starts at the amino (N) terminus and ends at the carboxy (C) terminus For example: Met-Val-Lys-Leu-Cys-Ala NC

5. Proteins Primary structure the sequence Secondary structure α-helices β-strands Turns Loops Tertiary structure Interactions between the secondary structure elements to form the structured protein Quaternary structure Dimers or multimers of proteins

6. Secondary structure The amino acids form four different secondary structure elements: α-helices β-strands Turns Loops

7. Secondary structure – α-helix N-terminus C-terminus

8. Secondary structure – β-strand A β-sheet consists of at least two β-strands which interact with each other Anti-parallelParallel

9. Secondary structure – Turn Turns connect the secondary structure elements

10. Secondary structure - Loop A loop is everything that has no defined secondary structure

11. Proteins Primary structure the sequence Secondary structure α-helices β-strands Turns Loops Tertiary structure Interactions between the secondary structure elements to form the structured protein Quaternary structure Dimers or multimers of proteins

12. Tertiary structure The secondary structure elements interact to form the structured protein

13. Proteins Primary structure the sequence Secondary structure α-helices β-strands Turns Loops Tertiary structure Interactions between the secondary structure elements to form the structured protein Quaternary structure Dimers or multimers of proteins

14. Quaternary structure Some proteins have to interact with each other to form dimers or multimers to get their functionality

15. Amino acids The (secondary and tertiary) structure of the protein depends on the primary structure and therefore on the sequence and therefore on the amino acids When you understand the amino acids, you understand everything!

16. Every amino acid has the same basic structure: the backbone with an amino group a C α a carboxyl group Amino acids – Structure α

17. Amino acids - Structure The C α is bound to an R group: the side chain different for each amino acid YASARA uses different colors for each kind of atom Note that the hydrogens are not shown in this picture α

18. Amino acids - Structure The C α is bound to an R group: the side chain different for each amino acid YASARA uses different colors for each kind of atom Note that the hydrogens are not shown in this picture α Carbon Nitrogen Oxygen

19. Amino acids - Structure The C α is bound to an R group: the side chain different for each amino acid YASARA uses different colors for each kind of atom Note that the hydrogens are not shown in this picture α

20. Amino acids - Structure The C α is bound to an R group: the side chain different for each amino acid YASARA uses different colors for each kind of atom Note that the hydrogens are not shown in this picture α Backbone

21. Amino acids - Structure The C α is bound to an R group: the side chain different for each amino acid YASARA uses different colors for each kind of atom Note that the hydrogens are not shown in this picture α Side chain Backbone

22. Amino acids – Peptide bond The amino acids can make polymers via peptide bonds Note that there remains a charge on the ends of the dipeptide

23. Amino acids – Codes There are 20 different amino acids One letter Three letter Name AAlaAlanine CCysCysteine DAspAspartate EGluGlutamate FPhePhenylalanine GGlyGlycine HHisHistidine IIleIsoleucine KLysLysine LLeuLeucine MMetMethionine NAsnAsparagine PProProline QGlnGlutamine RArgArginine SSerSerine TThrThreonine VValValine WTrpTryptophan YTyrTyrosine

24. Amino acids – Properties Each side chain has different structural and chemical properties Hydrophobicity Electric charge Size Sulfur containing Secondary structure preference Polar Alcoholic Aliphatic Aromatic Etc.

25. Amino acids – Properties Amino acids are not easily put into boxes according to their properties Every amino acid belongs to several categories Every amino acid is unique

26. Amino acids – Hydrophobicity Hydro = water; phobe = fear; phile = love Some amino acids like to stick into water (hydrophilic) Asp, Glu, His, Lys, Asn, Gln, Arg Some amino acids like to stick to each other (hydrophobic) Ala, Cys, Phe, Ile, Leu, Met, Pro, Val, Trp And some are inbetween Gly, Ser, Thr, Tyr

27. Amino acids – Hydrophobicity Hydrophobicity is the most important property It drives the folding of a protein The sticky amino acids glue together The non-sticky amino acids point to the water The waters must be ‘happy’

28. Amino acids - Hydrophobicity Water molecules are quite happy on their own Introduction of a fatty acid makes the waters around it unhappy They cannot make all hydrogen bonds They are bound in a “cage” around the fatty acid tail Hydrophilic head Hydrophobic tail

29. More fatty acids will glue together The total hydrophobic surface will be smaller More waters will be happy Amino acids - Hydrophobicity ( Not scaled!!! )

30. More fatty acids will glue together The total hydrophobic surface will be smaller More waters will be happy Amino acids - Hydrophobicity ( Not scaled!!! )

31. Amino acids – Electric charge LysArg AspGlu Positive, neutral and negative: His Depending on the environment His Positive: Lys, Arg Blue nitrogens Negative: Asp, Glu Red oxygens

32. Amino acids – Size Small amino acids Ala, Cys, Gly, Pro, Ser, Thr, Val Smallest: Gly Inbetween Asp, Ile, Leu, Asn Large amino acids Glu, Phe, Lys, Gln, Arg, Trp, Tyr Largest: Trp Gly Trp

33. Amino acids – Sulfur containing Cys and Met contain sulfur The sulfur of Cys is very reactive can make sulfur bridges with other cysteines CysMetSulfur bridge

34. Amino acids – Secondary structure preference Most amino acids have a secondary structure preference for helices strands or turns

35. Residues that are good for a helix Ala, Met, Glu, Leu, Lys (KAMEL) Residues that are good for strands Val, Ile, Thr, Trp, Tyr, Phe (WYFI-TV) Residues that are good for turns Pro, Ser, Asp, Asn, Gly (PSDNG) Amino acids – Secondary structure preference

36. It is all about amino acids MSQSTQTNEF LSPEVFQHIW DFLEQPIC Sequence Secondary structure elements M S Q ST Q T NE F LSP E V F QHI W D F L EQ P R IC All different properties Secondary structure preference Hydrophobicity Hydrogen bonds Charge interactions Tertiary structure (folded protein)