3 Proteins

本章的內(nèi)容是蛋白質(zhì)，一共分為五小節(jié)：本節(jié)a部分主要講述蛋白質(zhì)的基本構(gòu)成以及氨基酸，bc部分則開始描述蛋白質(zhì)的高級結(jié)構(gòu)。下一節(jié)將繼續(xù)討論蛋白質(zhì)的高級結(jié)構(gòu)以及蛋白質(zhì)折疊。本章的第三節(jié)將討論蛋白質(zhì)的調(diào)節(jié)與控制。第四五節(jié)將以不同的蛋白質(zhì)實(shí)驗(yàn)室方法作為第三章的結(jié)尾。如果有不太明白的或者有錯誤的地方隨時(shí)來找UP主喔~ 文集本部分的參考文獻(xiàn)Essential Cell Biology, 5th ed. Alberts, et al. 2019. 部分內(nèi)容來自khanacademy與維基百科.

封面圖：https://cdn1.byjus.com/biology/2017/08/30063857/Proteins-Structure.jpg

3a Proteins Overview & Amino acids

Some protein functions

????Enzyme (catalysts) -?Eg digestive enzymes, DNA polymerase

????Structural proteins - shape & protection -?Eg keratin in skin and hair, actin in cells

????Signals -?Eg hormones, Neurotransmitters

????Binding proteins -?Eg receptors, hemoglobin

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Specific structures are required for function! (eg to bind substrate!)

????????Structures need to be stable but also dynamic (change when necessary)

Structures:

????????Amino acids - polymerize into polypeptide chain (covalent bonds)

????????Polypeptide chain assembles into a folded protein

????????Several proteins associate into a protein complex

Individual polypeptide chain alone is called the monomer

????????Or a subunit in the protein complex (di-/tri-/tetra- mer)

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Amino Acids

????Central α?carbon attached to 4 groups:

????????- Amino group [at?pH 7 gain proton]

????????- Carboxylic acid?[at pH 7 lose proton]

????????- H

????????- Side chain (R)

Four classes of side chains

????Positively charged - ionic

????Negatively charged - ionic

????Polar - H-bond

????Non-polar - hydrophobic

????20 amino acids in total, each one has a 3-letter code

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Four interesting amino acids

????????- Histidine (His, H)

????????????pKa is about 7 (about half protonated at pH=7)

????????????Can be both a H+ donor and acceptor

????????????Useful in acid-base catalysis - Histidine can be both the source and sink for protons in acid-base catalysis reactions - the substrate becomes protonated and deprotonated during the reaction.

?????????- Proline (Pro, P)

????????????Side chain is covalently bound backbone in two places

????????????????Connected to both the alpha carbon and the N atom.

????????????????Other amino acids - side chain only connected to Cα

????????????????Proline backbone position is constrained. It is fixed into a rigid bend. (Bend angle)

????????- Glycine (Gly, G)

????????????????Glycine’s side chain is only an H, smallest amino acid

????????????????Glycine fits in places in proteins where other amino acids could not fit

????????- Cysteine (Cys, C)

????????????????Has a sulfhydral group (end of the chain) that can undergo redox reactions

????????????????-SH + HS- →oxidation→ -S-S- (disulfide bond, covalent)

????????????????Methionine (Met, M): S in the middle of the side chain, not chemically interesting.

????????????????Two Cysteines can be oxidized to form a covalent disulfide bond (within or between polypeptides).

????????????????Disulfides - only extracellular proteins - stabilize protein structures outside the cell (no molecular oxygen inside of the cell).

????????????????Hair - has S - smiles so bad when burn.

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3b Peptide Backbone

Levels of protein structure:

????Primary structure - linear sequence - amino acid residues

????Secondary structure - local folding - α?helix / β sheet

????Tertiary structure - global folding - polypeptide chain

????Quaternary structure - protein complex - assembled subunits

Bonds:

????Primary: covalent, peptide bonds

????Secondary/Tertiary/Quaternary: non-covalent

????Tertiary/Quaternary: also disulfide bonds which is covalent

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Amino acids have full charges (+/-)

Peptide bond is uncharged but polar

????????Bottom O partial negative

????????Top H partial positive

An amino acid peptide:

????????Has an amino-terminal end & a carboxyl-terminal end

????????Peptide backbone is polar, with full charges on at N- and C- terminus

????????N-terminus is always shown to the left!

????????One peptide bond will give a polar group

3c Secondary structure

????????Protein folding is automatic, amino acid sequence determines 3-D structure!

Secondary structures

????????Local interactions - only backbone atoms are shown

????????H-bonds between backbone groups: carboxyl group O --- H amino acid group

α?helix: H bonds form to an amino acid that is 1 turn ahead within the helix

????Amino & Carboxyl - 4 positions away

????eg keratin protein in hair is α?helical

β sheet: H bonds form between β?strands

????Usually twisted, not completely flat

????Parallel: with same C-N terminal directions

????Antiparallel: with alternative C-N terminal directions

????eg Skill protein consist of stacks of β-sheet

Side chains

????α?helix: outside the helix

????β sheet: both above / below the sheet

Loops

????Surface of the protein

????L?oops are different and irregular

α?helix?and β sheet?(and loop) can together appear in one protein [most are these!]. These structure are stable - maintain structure through H-bonds. Side chains group can vary, only backbone groups fold.

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Ribbon diagram

????Traces backbone, highlight secondary structures

????Deceptively open

Space-filling model

????Realistic atom sizes, illustrates tight packing

????Hard to see details, but more accurate

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Tightly pack proteins structured more stable than loosely packed ones.

????????Thight packing - no space between atoms - allows dispersion forces have there maximum effect.