Protein Structure Timothy G. Standish, Ph. D.

The Genetic Code U C A G U C A G S E C O N D B A S E F I R S T B A E T Neutral Non-polar Polar Basic Acidic S E C O N D B A S E U C A G F I R S T B A E U UUU UUC UUA UUG UCU UCC UCA UCG UAU UAC UAA UAG UGU UGC UGA UGG U C A G T H I R D B A S E Phe Tyr Cys Ser Stop Leu Stop Trp C CUU CUC CUA CUG CCU CCC CCA CCG CAU CAC CAA CAG CGU CGC CGA CGG U C A G His Leu Pro Arg Gln† A AUU AUC AUA AUG ACU ACC ACA ACG AAU AAC AAA AAG AGU AGC AGA AGG U C A G Asn† Ser Ile Thr Lys Arg †Have amine groups Met/ start G GUU GUC GUA GUG GCU GCC GCA GCG GAU GAC GAA GAG GGU GGC GGA GGG U C A G Asp Val Ala Gly* *Listed as non-polar by some texts Glu

Different Amino Acid Classes OH H O H2N C Alanine C OH H O HS H2N Cysteine Non-polar Polar OH O H H2N C R Generic Acid Amine C OH H O H+N H2N NH Histidine H H2N C O OH Aspartic acid ? Acid Basic

Non-Polar Amino Acids OH O H H2N C Glycine Methionine OH O H H2N C H3C Valine OH O H H2N C H3C CH3 Leucine OH O H H2N C H3C CH3 Alanine OH H O H2N C Tryptophan OH O H H2N C NH Phenylalanine OH H O H2N C Isoleucine OH O H H2N C H3C Proline OH O H H2N+ C H2C CH2

Polar Amino Acids Tyrosine HO H O H2N C OH Serine OH O H H2N C HO CH3 Threonine OH O H H2N C Glutamine H H2N C O OH NH2 Cysteine C OH H O HS H2N Asparagine H H2N C O OH NH2

Acidic Amino Acids Aspartic Glutamic acid acid H2N H2N OH OH C C H H O

Basic Amino Acids O Histidine H2N OH O Lysine C H2N OH C O Arginine H NH Lysine OH O H H2N C +H3N Arginine OH O H H2N C N +H2N NH2

Levels Of Protein Organization Primary Structure - The sequence of amino acids in the protein Secondary Structure - The formation of a helices and b pleated sheets due to hydrogen bonding between the peptide backbone Tertiary Structure - Folding of helices and sheets influenced by R groups Quaternary Structure - The association of more than one polypeptide into a protein complex influenced by R groups

Levels Of Protein Organization Primary Structure Met-Gly-Ala-Pro-His-Ile-Asp-Glu-Met-Ser-Thr-...

Glyceraldehyde-3-Phosphate Dehydrogenase Primary Structure The Mycoplasma genitalium G-3P dehydrogenase protein sequence: MAAKNRTIKV AINGFGRIGR LVFRSLLSKA NVEVVAINDL TQPEVLAHLL KYDSAHGELK RKITVKQNIL QIDRKKVYVF SEKDPQNLPW DEHDIDVVIE STGRFVSEEG ASLHLKAGAK RVIISAPAKE KTIRTVVYNV NHKTISSDDK IISAASCTTN CLAPLVHVLE KNFGIVYGTM LTVHAYTADQ RLQDAPHNDL RRARAAAVNI VPTTTGAAKA IGLVVPEANG KLNGMSLRVP VLTGSIVELS VVLEKSPSVE QVNQAMKRFA SASFKYCEDP IVSSDVVSSE YGSIFDSKLT NIVEVDGMKL YKVYAWYDNE SSYVHQLVRV VSYCAKL

Protein Secondary Structure The peptide backbone of DNA has areas of positive charge and negative charge These areas can interact with one another to form hydrogen bonds The result of these hydrogen bonds are two types of structures: a helices b pleated sheets

Protein Secondary Structure: a Helix + - C O OH N H HO

Protein Secondary Structure: a Helix + - C O OH N H HO

Protein Secondary Structure: a Helix R groups stick out from the a helix influencing higher levels of protein organization

Yeast Cytochrome C Oxidase Subunit IV Leader P L T C S I K F A M Q Yeast Cytochrome C Oxidase Subunit IV Leader First 12 residues are sufficient for transport to the mitochondria Neutral Non-polar Polar Basic Acidic MLSLRQSIRFFKPATRTLCSSRYLL This leader sequence probably forms an a helix This would localize specific classes of amino acids in specific parts of the helix There are about 3.6 amino acids per turn of the helix with a rise of 0.54 nm per turn

Protein Secondary Structure: b Pleated Sheet

Protein Secondary Structure: b Pleated Sheet

Levels Of Protein Organization Tertiary Structure Tertiary structure results from the folding of a helices and b pleated sheets Factors influencing tertiary structure include: Hydrophobic/hydrophilic interactions Hydrogen bonding Disulfide linkages Folding by chaperone proteins

G-3-P Dehydrogenase Tertiary Structure Picture source: SWISS-PROT

Levels Of Protein Organization Quaternary Structure Quaternary structure results from the interaction of independent polypeptide chains Factors influencing quaternary structure include: Hydrophobic/hydrophilic interactions Hydrogen bonding The shape and charge distribution on associating polypeptides

G-3-P Dehydrogenase from Bacillus stearothermophilus Skarzynski, T., Moody, P. C. E., Wonacott, A. J.: Structure of Holo-Glyceraldehyde-3-Phosphate Dehydrogenase from Bacillus Stearothermophilus at 1.8 Angstroms Resolution. J.Mol.Biol. 193 pp. 171 (1987) Picture source: SWISS-PROT

The Globin Gene Family a b Globin genes code for the protein portion of hemoglobin In adults, hemoglobin is made up of an iron containing heme molecule surrounded by 4 globin proteins: 2 a globins and 2 b globins a b Fe During development, different globin genes are expressed which alter the oxygen affinity of embryonic and fetal hemoglobin

Haemoglobin Luisi, B., Shibayama, N.: Structure of Haemoglobin in the Deoxy Quaternary State with Ligand Bound at the Alpha Haems. J.Mol.Biol. 206 pp. 723 (1989) Picture source: SWISS-PROT

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