1 1 Chapter 7 - Protein F unction Important Principles • Key features of protein function demonstr ated by O 2 -bind ing proteins (Hb, Mb), Immune system proteins and Muscle proteins • Proteins are flexible, not rigid • Protein function often depends on their interaction with ligands 2 • Myoglobin & Hemoglobin contain a heme prosthetic group that binds 0 2 reversibly • Hemoglobin is a multi- subunit protein that binds 0 2 cooperatively • Hb binds H + , CO 2 and 2,3 bisphosphoglycerate in a manner that a ffe cts the affinity for 0 2 • Sickle-cell anemia illustrates the importance of conformation to function 3 • The immune system utilizes extremely specific interactions between proteins and foreign molecules to protect the organism • Protein flexibi lity a nd intera ctions are illustra ted by the cyclic conf ormational changes that cause muscles to contract 4 Protein function • Protein function al most always de pend s on interactions with other molecules (ligands) – H + , O 2 , ATP, lipids, peptides, pro teins, RNA, etc. • Transient nature of protein-ligand interactions (noncovalent) allows for flexibility in response • Ligand s bind at binding sites – Complementary in shap e, size, c harg e, hydrop hobic or hydrophilic character of ligand 5 • Protein-ligand inte rac ti on is specific - very selective binding • proteins may ha ve separ ate binding sites for multiple ligands • Proteins are flexible - subtle or dramatic changes in structure to acc omodate ligands • Binding coupled to conformational changes - “ind uced fit” 6 • In multimeric protei ns, conformational changes often “contagious” • Special cases of Enzymes – Ligands = subs trat es – Binding site = cat aly tic site or “active site”
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
1
1
Chapter 7 - Protein Function
Important Principles
• Key features of protein function demonstratedby O2-binding proteins (Hb, Mb), Immunesystem proteins and Muscle proteins
• Proteins are flexible, not rigid
• Protein function often depends on theirinteraction with ligands
2
• Myoglobin & Hemoglobin contain a hemeprosthetic group that binds 02 reversibly
• Hemoglobin is a multi-subunit protein that
binds 02 cooperatively
• Hb binds H+, CO2 and 2,3 bisphosphoglyceratein a manner that affects the affinity for 02
• Sickle-cell anemia illustrates the importance ofconformation to function
3
• The immune system utilizes extremely specificinteractions between proteins and foreignmolecules to protect the organism
• Protein flexibility and interactions areillustrated by the cyclic conformationalchanges that cause muscles to contract
4
Protein function
• Protein function almost always depends oninteractions with other molecules (ligands)– H+, O2, ATP, lipids, peptides, proteins, RNA, etc.
• Transient nature of protein-ligand interactions(noncovalent) allows for flexibility in response
• Ligands bind at binding sites– Complementary in shape, size, charge,
hydrophobic or hydrophilic character of ligand
5
• Protein-ligand interac tion is specific - veryselective binding
• proteins may have separate binding sites formultiple ligands
• Proteins are flexible - subtle or dramaticchanges in structure to accomodate ligands
• Binding coupled to conformational changes -“induced fit”
6
• In multimeric proteins, conformationalchanges often “contagious”
• Special cases of Enzymes– Ligands = substrates– Binding site = catalytic site or “active site”
2
7
Reversible binding of ligands - 02 proteins
• Myoglobin (Mb) & Hemoglobin (Hb)– Most studied, best understood– Illustrate most aspects of ligand binding
Mb
Fig 7.3
Hb
Fig 6.23a
8
Oxygen binding proteins (Mb & Hb)
Proteins evolved to store & transport gases
– O2 poorly soluble
– Diffusion through tissues low
O2 bound to Heme Prosthetic group
– No αα side chain suited for binding of O2
– Fe & Cu bind O2, but form free radicals
– O2-binding properties of Fe exploited bysequestering it in less reactive form
9
Heme - organic ring structure whichbinds single Fe2+
Sequestering heme prevents irreversibleoxidation of Fe2+ to Fe3+
Fig 7.1a Fig . 7.1b
10
Myoglobin (Mb) - Single O2 binding protein
• Mr = 16,700
• Found in almost allmammals
• Primarily muscle tissue
• particularly abundantin diving mammals
• 153 αα’s; 1 hememolecule
• Member of globinfamily of proteins
11
Protein-ligand interac tions can be describedquantitatively
• Mb function depends on ability to bind/release
O2 where needed
• Quantitative description central to
understanding
12
Equations of the form x=__y�__ describe hyperbolas y + z
[L] at which 1/2 of the available binding sitesare occupied (θ = 0.5) = 1/Ka=Kd
3
13
For Mb, Kd = [O2] ([L]) at which 1/2 theavailable binding sites are occupied
With O2, we’re dealing with volatile substance,use partial pressure as substitue for