Objectives Objectives List the properties of carbon that define it as List the properties of carbon that define it as the element of biological molecules the element of biological molecules Identify important functional groups associated Identify important functional groups associated with biological molecules with biological molecules Describe the structure and function of lipids Describe the structure and function of lipids Describe the structure and function of Describe the structure and function of carbohydrates carbohydrates Describe the structure and function of nucleic Describe the structure and function of nucleic acids acids Describe the structure and function of proteins Describe the structure and function of proteins – Describe the structural levels of Describe the structural levels of organization of proteins organization of proteins – Define protein domains and protein families Define protein domains and protein families – Define protein motifs and list examples Define protein motifs and list examples – Describe how chaperones aid in the folding Describe how chaperones aid in the folding of proteins of proteins
Transcript
ObjectivesObjectivesList the properties of carbon that define it as the element List the properties of carbon that define it as the element of biological moleculesof biological moleculesIdentify important functional groups associated with Identify important functional groups associated with biological moleculesbiological moleculesDescribe the structure and function of lipidsDescribe the structure and function of lipidsDescribe the structure and function of carbohydratesDescribe the structure and function of carbohydratesDescribe the structure and function of nucleic acidsDescribe the structure and function of nucleic acidsDescribe the structure and function of proteinsDescribe the structure and function of proteins– Describe the structural levels of organization of Describe the structural levels of organization of
proteinsproteins– Define protein domains and protein familiesDefine protein domains and protein families– Define protein motifs and list examplesDefine protein motifs and list examples– Describe how chaperones aid in the folding of Describe how chaperones aid in the folding of
proteinsproteins
Chemical Composition of CellsChemical Composition of CellsWhat are the common elements found in cell macromolecules?
CarbonCarbon•Atomic number = 6 •Atomic weight =12•How many protons? Electrons? Neutrons?•Why does carbon form 4-covalent bonds?•What other elements form covalent bonds with carbon
HydrocarbonsHydrocarbons
Functions?
Hydrophobic or hydrophilic?
Functional GroupsFunctional Groups
Functional Groups: PhosphatesFunctional Groups: PhosphatesWhere do you find phosphodiester bonds?
ClassificationsClassifications•Macromolecules: Examples?; most have short half lives•Monomers: Exist as pools in cells; building blocks •Metabolic intermediates: Examples?•Miscellaneous functions: Vitamins, hormones, cofactors, energy carriers
Structural and functional biological molecules in cells
CarbohydratesCarbohydratesFunctions– Structural components of cells and tissues
Glycoproteins and glycolipids (animal cells)Cellulose (plant cells & lower invertebrates)Chitin (exoskeleton; insects and crustaceans)Peptidoglycan (bacterial cell wall)Glycosaminoglycans (GAGs): extracellular matrix
– Short-term fuel source for cells (2000 Cal)Structure– Monosaccharides- monomers of 5-7 carbons– Polymers of monosaccharide subunits
Oligosaccharides (few) and polysaccharides (many)
MonosaccharidesMonosaccharides•5-7 carbons with two or more OH groups and a ketone or aldehyde group: Pentoses, Hexoses, Heptoses•Form pyranose rings in water (reaction between ketone or aldehyde and an OH
Stereoisomers
PolymerizationPolymerizationGlycosidic bonds formed between OH groups
•Oligosaccharides: small chains
• Glycoproteins & glycolipids
• Cell markers• Cell adhesion
•Polysaccharides: large polymers
• Stored energy• Structural components
Alpha/Beta LinksAlpha/Beta LinksEnzymes recognize different linkages
(1-2)
(1-2)
PolysaccharidesPolysaccharidesGlycogen•Highly branched polymer of glucose: (1-4); branches every 8-10 residues via (1-6) linkages
Starch (amylose)•Unbranched polymer of glucose; (1-4) linkages
Cellulose•Unbranched polymer of glucose; (1-4) linkages
LipidsLipidsGreasy oils; non-polar, hydrophobic or amphipathic
Triglycerides Phospholipids
Sterols
Fatty AcidsFatty Acids•Hydrocarbon chains of up to 36 (ave 14-20) carbons; amphipathic (why?)
Where do you find fatty acid tails? What properties do they contribute to the molecules?What are the structural and functional differences between saturated and unsaturated molecules?
TriglyceridesTriglycerides•Structure & function? •Where do you find triglycerides in the human body?
Saturated: animal fat (butter & lard)Unsaturated: oils (C=C in cis configuration)Trans-Fats: hydrogenated oils; hydrogenation creates C=C in trans configuration
PhospholipidsPhospholipids
Phosphatidylcholine
StructureFunction Examples
SterolsSterols•Structural characteristics
•Function
•Cholesterol•LDL vs HDL
Nucleic AcidsMonomeric units?Monomeric units?What are the bonds in What are the bonds in the sugar phosphate the sugar phosphate backbone?backbone?What is the net What is the net charge?charge?What characterizes 3’ What characterizes 3’ and 5’ endsand 5’ endsIs this DNA or RNAIs this DNA or RNA
Nitrogenous BasesNitrogenous Bases
DeNovo and salvage DeNovo and salvage pathwayspathwaysWhich bases are Which bases are found in RNA and found in RNA and DNADNAWhich bases form Which bases form hydrogen bonds in hydrogen bonds in DNADNA
Nucleosides & NucleotidesNucleosides & Nucleotides•Nucleoside?•Nucleotide?•Nomenclature?•How do NTPs & dNTPs differ?
ProteinsProteinsMost diverse in structure and functionMost diverse in structure and function– Over 10,000 kinds of proteins per cellOver 10,000 kinds of proteins per cell– High degree of specificityHigh degree of specificity
Polymers of amino acids; Most range 30 to 10,000 Polymers of amino acids; Most range 30 to 10,000 amino acid amino acid residues / chain (Ave: 450) / chain (Ave: 450)– Longest protein is muscle titan (30,000 amino acids) Longest protein is muscle titan (30,000 amino acids)
Functional only when folded into “native” (tertiary or Functional only when folded into “native” (tertiary or quaternary) structure; function by interacting with other quaternary) structure; function by interacting with other molecules; Globular or fibrous in structuremolecules; Globular or fibrous in structureFunctional proteins may contain one or more polypeptide Functional proteins may contain one or more polypeptide chainschainsModifications may change conformation of native Modifications may change conformation of native structure and functionstructure and functionMay be conjugated to other molecules; glycoproteins, May be conjugated to other molecules; glycoproteins, lipoproteins and nucleoproteinslipoproteins and nucleoproteins
• Proteins are globular or fibrous in nature• Globular: Compact shapes; Most intracellular and secreted
proteins: Examples• Fibrous: Elongated strands or sheets; resist pulling and
tearing: Examples
Functional DiversityFunctional Diversity
Amino AcidsAmino Acids•Common structure shared by all amino acids•20 different amino acids differ in R group•R-groups influence chemical and physical properties•Exist as Zwitterions in nature
D & L IsomersD & L Isomers•Stereoisomers: Different spatial arrangements of 4 different groups bound to alpha carbon•Most naturally occurring amino acids exist as L-amino acids Eukaryotic proteins contain L-amino acids
Amino Acids
Weakly acidic or basic at neutral pH
Nonpolar associate with each other in protein core via hydrophobic and van der Waals interactions
PolypeptidePolypeptide•Peptide bonds link alpha carbons of amino acids (backbone)•R groups stick out as side chains.•Synthesized and read N terminus to C terminus
Primary StructurePrimary StructureSequence of amino acid residues (N to C)Encoded by gene sequencesDetermines final structure and function
Secondary: Secondary: Helix Helix•How is the structure stabilized?•Highly extendible: Example wool•Connected by hinges, turns, loops & extensions•Location of R groups? Why are most Right handed?
May be amphipathic
22oo: : -Pleated Sheets-Pleated Sheets•How is the structure stabilized?•What do the arrows mean? Parallel or anti-parallel?•Provide tensile strength to proteins (Example: silk)•Where are the R groups?
Native StructureNative StructureStabilized by non-covalent and covalent interactions primarily between non-contiguous R groups
Tertiary Structure• Native structure of proteins composed of single
polypeptide chain• Example: Myoglobin- What is the major secondary
structure?
Quaternary Structure• Native structure of proteins composed of two or more
polypeptide chains (subunits)• Heterodimers or homodimers• Example: Immunoglobulins• How are chains stabilized?
Protein DomainsProteins composed of two or more distinct regionsFunctional regions that fold independently of each otherEncoded by exonsMay be conserved and found in other proteins
• Proteins with shared Proteins with shared structural featuresstructural features
• Immunoglobulin Immunoglobulin superfamily of superfamily of proteinsproteins
• All contain All contain immunoglobulin-like immunoglobulin-like domainsdomains
Protein Families
Protein MotifsProtein Motifs•Definition: Evolutionarily conserved structural characteristics shared among proteins with similar functions•Generally contained within a functional domain
In signaling domain
ITAM
Zinc Finger
Protein-Protein Interactions
Figure 2.40a.b
Ag Epitope
Ag paratope
Function by interacting with other proteins or macromolecules
Complementary surfaces fit together
Most are dynamic interactions
Protein NetworksProtein NetworksHub proteins interact with multiple proteins to form huge protein complexes
May act with multiple proteins one at a time
Conformational Changes• Non-random movements triggered by binding of a
specific molecule: substrates, other proteins or by post-translational modification of a protein
• May occur with protein activity or alter protein activity
Post-translational ModificationsPost-translational Modifications• Modifications change conformation & function of proteins• Phosphorylation of Tyr, Ser, Thr amino acids – signaling• Cleavage and activation of pro-enzymes – apoptosis
Protein FoldingProtein FoldingDefined by 1Defined by 1oo structure structureFold into most Fold into most thermodynamically stable thermodynamically stable formformAutomatic process for Automatic process for small proteinssmall proteinsLarger proteins may need Larger proteins may need helphelpAbnormal folding linked to Abnormal folding linked to protein aggregates and protein aggregates and disease disease
Chaperones & Chaperonins• Families of proteins that aid in proper folding to proteins• Chaperones- many are heat shock proteins
• Bind to hydrophobic regions of newly synthesized proteins preventing improper aggregation and proper folding and association with other polypeptides
• Chaperonins- Barrel-like structures that provide favorable environment for folding
GroEL ChaperoninGroEL Chaperonin•Found in prokaryotes; one of most studied•Complex of 14 protein subunits: form double barrel structure•Acts in conjunction with GroES; Energy dependent
Protein RecyclingProtein Recycling
Proteosomes
• All proteins have a half-life• Several cellular re-cycling pathways• Proteosomes & autophagy – cytosolic proteins• Endocytic pathway – membrane proteins
