生化生物化學(xué)第2

1、Chapter 2:Protein Composition and Structure崔莉cuiliBiochemistrySixth EditionBerg Tymoczko StryerIntroductionProtein: 生物功能的主要載體，于身體各個(gè)組織Ø Macromolecules(數(shù)千數(shù)十萬）Ø Versatile （組成-結(jié)構(gòu)-功能）Ø Structure and Function（激素、酶）Maintain bloodsugarat appropriate levelsStructure and Crystals of human insul

2、in. IOUTLINES結(jié)構(gòu)單元、聚合方式以及聚合后的形成的結(jié)構(gòu)形態(tài)1. Proteins Are Built from a Repertoire of 20 Amino Acids2. Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains3. Secondary Structure: Polypeptide Chains Can Fold into Regular Structures Such As the Alpha Helix, the Beta Sheet, and

3、 Turns and LoopsOUTLINES4. Tertiary Structure: Water-Soluble Proteins Fold into Compact Structures with Nonpolar Cores5. Quaternary Structure: Polypeptide Chains Can Assemble into Multisubunit Structures6. The Amino Acid Sequence of a Protein Determines Its Three-Dimensional StructureOUTLINES結(jié)構(gòu)單元、聚合

4、方式以及聚合后的形成的結(jié)構(gòu)形態(tài)1. Proteins Are Built from a Repertoire of 20 Amino Acids2. Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains3. Secondary Structure: Polypeptide Chains Can Fold into Regular Structures Such As the Alpha Helix, the Beta Sheet, and Turns and Loops1.Pr

5、oteins Are Built from a Repertoire of 20 Amino AcidsDNA的結(jié)構(gòu)單元：核苷酸 4 種Versatile（組成-結(jié)構(gòu)-功能）蛋白質(zhì)的結(jié)構(gòu)單元：氨基酸 20 種1.Proteins Are Built from a Repertoire of 20 Amino Acids蛋白質(zhì)的結(jié)構(gòu)單元SconfigurationFigure 2.4 The L and D isomers of amino acids. L and D isomers are mirror images of each other. Only L aminoacids are

6、found in proteins1.Proteins Are Built from aRepertoire of 20 Amino AcidsDistinctive R goroup: sides, shape, charge, hydrogenbonding capacity, hydrophobic character.兼性離子Ionization state as a function of pH.1.Proteins Are Built from a Repertoire of 20 Amino AcidsDistinctive R goroup:Ø 按側(cè)鏈性質(zhì)劃分：

7、16;按側(cè)鏈結(jié)構(gòu)劃分：Aliphatic（15）Aromatic（3）Heterocyclic（2）I）Non-polar （8）Aliphatic（5）Aromatic（2）Heterocyclic（1）II）Polar（12）活性基團(tuán)Uncharged（1+1+2+3） Acidic （2）Basic （3）1.Proteins Are Built from aRepertoire of 20 Amino Acids（1）非極性氨基酸：R基為脂肪側(cè)鏈（5）：丙氨酸纈氨酸亮氨酸異亮氨酸甲硫氨酸1.Proteins Are Built from aRepertoire of 20 Amino

8、Acids（1）非極性氨基酸：R基為脂肪側(cè)鏈（5）：名稱你結(jié)構(gòu)與功能特點(diǎn)異亮氨酸、亮氨酸、纈氨酸均含有較大的疏水側(cè)鏈，其剛性結(jié)構(gòu)特征及疏水相互作用都對蛋白折 疊有重要的影響力，常作為水溶性蛋白的內(nèi)部支撐結(jié)構(gòu)甲硫氨酸是多肽鏈生物的起始氨基酸；參與體內(nèi)含硫化合物代謝及甲基化 反應(yīng)丙氨酸轉(zhuǎn)氨酶中的氨基供體1.Proteins Are Built from a Repertoire of 20 Amino Acids（1）非極性氨基酸：R基為雜環(huán)脂肪側(cè)鏈（1）：脯氨酸名稱結(jié)構(gòu)與功能特點(diǎn)N原子在雜環(huán)中移動(dòng)的脯氨酸度受到限制，常位于多肽鏈的轉(zhuǎn)角處1.Proteins Are Built from a Re

9、pertoire of 20 Amino Acids（1）非極性氨基酸：R基為芳香側(cè)鏈（2）：苯丙氨酸色氨酸名稱結(jié)構(gòu)與功能特點(diǎn)苯丙氨酸、色氨酸側(cè)鏈結(jié)構(gòu)大且極性較弱或無極性，常位于水溶性蛋白的內(nèi)部1.Proteins Are Built from a Repertoire of 20 Amino Acids（2）極性氨基酸：不帶電荷（7,中性氨基酸）：天冬酰胺谷胺酰胺甘氨酸1 (-H)半胱氨酸+1 (-SH)酪氨酸絲氨酸+3 (-OH)蘇氨酸+ 2 (-CONH2)1.Proteins Are Built from a Repertoire of 20 Amino Acids（2）極性氨基酸：不

10、帶電荷（7,中性氨基酸）：名稱結(jié)構(gòu)與功能特點(diǎn)半胱氨酸氧化狀態(tài)下，多肽鏈中不相鄰的兩個(gè)半胱氨酸通過二硫鍵相連，增強(qiáng)蛋白質(zhì)結(jié)構(gòu)的性；巰基易與重金屬離子結(jié)合酪氨酸側(cè)鏈結(jié)構(gòu)大且極性較弱，常位于水溶性蛋白的內(nèi)部甘氨酸是唯一不不對稱結(jié)構(gòu)的氨基酸，有較大的旋轉(zhuǎn)度，賦予多肽鏈更多的柔性；是最小的氨基酸，能夠于空間致密的蛋白質(zhì)中，如膠原絲氨酸、蘇氨酸側(cè)鏈短，所含羥基常作為酶反應(yīng)中的供氫體；親水性強(qiáng)，位于水溶性蛋白表面天冬酰胺、谷氨酰胺極性酰胺鍵一般不具有反應(yīng)性，作為氫鍵的受體和供體，在堿性和溫度下不，會(huì)發(fā)生脫酰胺反應(yīng)，形成酸性側(cè)鏈1.Proteins Are Built from a Repertoire of

11、 20 Amino Acids（2）極性氨基酸：帶正電荷（3，堿性氨基酸）：賴氨酸精氨酸組氨酸1.Proteins Are Built from aRepertoire of 20 Amino Acids（2）極性氨基酸：帶正電荷（3，堿性氨基酸）：名稱結(jié)構(gòu)與功能特點(diǎn)組氨酸咪唑基團(tuán)容易發(fā)生質(zhì)子化，進(jìn)而影響其所在的蛋白質(zhì)構(gòu)象，因此是許 多蛋白質(zhì)功能的調(diào)節(jié)機(jī)制賴氨酸、精氨酸有帶正電荷的柔性側(cè)鏈，常作為蛋白的親水表面，且易于結(jié)合帶有負(fù) 電荷的其他，如DNA1.Proteins Are Built from a Repertoire of 20 Amino Acids（2）極性氨基酸：帶負(fù)電荷（2，酸

12、性氨基酸）：天冬氨酸谷氨酸名稱結(jié)構(gòu)與功能特點(diǎn)天冬氨酸、谷氨酸攜帶強(qiáng)負(fù)電荷，常位于水溶性蛋白的表面；可結(jié)合帶正電荷的或金屬離子1.Proteins Are Built from a Repertoire of 20 Amino Acids蛋白質(zhì)中的氨基酸依據(jù)極性的分類總結(jié)類 別主要氨基酸非極性脂肪族氨基酸丙氨酸、纈氨酸、亮氨酸、異亮氨酸、甲硫氨酸芳香族氨基酸苯丙氨酸雜環(huán)氨基酸脯氨酸、色氨酸極性不帶電荷的氨基酸（中性氨基酸）甘氨酸、絲氨酸、半胱氨酸、蘇氨酸、天冬酰胺、谷氨酰胺、酪氨酸帶負(fù)電荷的氨基酸（酸性氨基酸）天冬氨酸、谷氨酸帶正電荷的氨基酸（堿性氨基酸）賴氨酸、精氨酸、組氨酸1.Protein

13、s Are Built from a Repertoire of 20 Amino AcidsOUTLINES結(jié)構(gòu)單元、聚合方式以及聚合后的形成的結(jié)構(gòu)形態(tài)1. Proteins Are Built from a Repertoire of 20 Amino Acids2. Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains3. Secondary Structure: Polypeptide Chains Can Fold into Regular Structures Su

14、ch As the Alpha Helix, the Beta Sheet, and Turns and Loops2. Primary Structure: Amino AcidsAre Linked by Peptide Bonds蛋白質(zhì)的一級結(jié)構(gòu)：N末端氨基酸 肽鍵肽鏈二硫鍵（共價(jià)鍵）C末端 牛胰島素2. Primary Structure: Amino Acids Are Linked by Peptide BondsPeptide-bond formation：肽鏈的骨架肽鍵：縮合脫水肽鏈：2. Primary Structure: Amino Acids Are Linked by

15、 Peptide BondsAmino acid sequences have direction.Amino acid sequences have direction. This illustration of the penta- peptide Try-Gly-Gly-Phe-Leu (YGGFL) shows the sequence from N- terminus to C-terminus.量：128；氨基酸殘基平均量：110氨基酸平均2. Primary Structure: Amino Acids Are Linked by Peptide BondsTrans and c

16、is peptide bonds.反式結(jié)構(gòu)為優(yōu)勢結(jié)構(gòu)Figure 2.25Trans and cis peptide bonds. The trans form isstrongly favored because of steric clashes that occur in the cis form.2. Primary Structure: Amino Acids Are Linked by Peptide BondsTrans and cis X-Pro bonds.因?yàn)榕鲎驳那闆r相似，所以兩種結(jié)構(gòu)的能量水平相似Figure 2.26 Trans and cis X-Pro bonds

17、. The energies of these forms are similar to one another because steric clashes occur in both forms.2. Primary Structure: Amino Acids Are Linked by Peptide BondsTypical bond lengths within a peptide unit.反式結(jié)構(gòu)的參數(shù)Figure 2.24 Typical bond lengths within a peptide unit. Thepeptide unit isshown in the tr

18、ans configuration.2. Primary Structure: Amino Acids Are Linked by Peptide Bonds:肽氮原子上的孤對電子與羰基具有共軛作用組成肽鍵的原子處于同一平面2. Primary Structure: Amino Acids Are Linked by Peptide BondsPlannar peptide bonds肽鍵具有部分雙鍵性質(zhì)，不能旋轉(zhuǎn)。多肽鏈柔軟但構(gòu)象受限肽Figure 2.23Peptide bonds are planar.In a pair of linked aminoacids, six atoms (

19、Ca, C, O, N, H, and Ca ) lie in a plane. Side chainsare shown as green balls.2. Primary Structure: Amino Acids Are Linked by Peptide BondsCa鍵的旋轉(zhuǎn)：兩個(gè)單鍵旋轉(zhuǎn),兩個(gè)平面之間形成的角度稱肽相鄰肽為扭角(Torsion angle)或二面角(dihedral angle)。 Ca-C ：y ;Ca-N ：f2. Primary Structure: Amino Acids Are Linked by Peptide BondsRotation about

20、bonds in a polypeptide.Figure 2.27 Rotation about bonds in a polypeptide. The structure of each amino acid in a polypeptide can be adjusted by rotation about two single bonds. Phi (f) is the angle of rotation about the bond between the nitrogen and the a-carbon atoms, whereas psi (y) is the angle of

21、 rotation about the bond between the a-carbon and the carbonyl carbon atoms.2. Primary Structure: Amino Acids Are Linked by Peptide Bonds(Left) A view down the bond between the nitrogen and the a-C atoms, showing how f is measured. (Right) A view down the bond between the a-C and the carbonyl carbon

22、 atoms, showing how y is measured.2. Primary Structure: Amino Acids Are Linked by Peptide BondsFigure 2.28 A Ramachandran diagram showing the values of f and y. Not all f and y values are possible without collisions between atoms. The most favorable regions are shown in dark green; borderline region

23、s are shown in light green. The structure on the right is disfavored because of steric clashes.2. Primary Structure: Amino Acids Are Linked by Peptide BondsComponents of a polypeptide chain：R基之間的相互作用能量的構(gòu)象2. Primary Structure: Amino Acids Are Linked by Peptide BondsThe formation of a disulfide bond：二

24、硫鍵氧化脫氫Figure 2.21Cross-links. The formation of a disulfide bondfrom two cysteine residues is an oxidation reaction.2. Primary Structure: Amino Acids Are Linked by Peptide BondsProteins Have Unique Amino Acid Sequences Specified by GenesFigure 2.22 Amino add sequence of bovine insulin.2. Primary Stru

25、cture: Amino Acids Are Linked by Peptide Bonds作用力 + 旋轉(zhuǎn) - 高級結(jié)構(gòu)Question and DiscussionOUTLINES結(jié)構(gòu)單元、聚合方式以及聚合后的形成的結(jié)構(gòu)形態(tài)1. Proteins Are Built from a Repertoire of 20 Amino Acids2. Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains3. Secondary Structure: Polypeptide Chain

26、s Can Fold into Regular Structures Such As the Alpha Helix, the Beta Sheet, and Turns and LoopsOUTLINES4. Tertiary Structure: Water-Soluble Proteins Fold into Compact Structures with Nonpolar Cores5. Quaternary Structure: Polypeptide Chains Can Assemble into Multisubunit Structures6. The Amino Acid

27、Sequence of a Protein Determines Its Three-Dimensional Structure3. Secondary Structure: a Helix, b Sheet, Turns and Loops一級結(jié)構(gòu) +蛋白的作用力 - 平衡 - 高級結(jié)構(gòu)3. Secondary Structure: a Helix, b Sheet, Turns and Loops蛋白結(jié)構(gòu)可視化數(shù)據(jù)庫： PDB ID： 2C81 3. Secondary Structure: a Helix, b Sheet, Turns and Loops維持三維結(jié)構(gòu)的作用力：3. Se

28、condary Structure: a Helix, b Sheet, Turns and Loops主鏈肽基之間形成最大數(shù)目的內(nèi)氫鍵，同時(shí)保氫鍵：持大多數(shù)能成氫鍵的側(cè)鏈處于蛋白質(zhì)與水相互作用。表面，將Ø蛋白質(zhì)二級結(jié)構(gòu)的主要作用力3. Secondary Structure: a Helix, b Sheet, Turns and Loops鏈間氫鍵鏈內(nèi)氫鍵蛋白質(zhì)結(jié)構(gòu)：-螺旋和-片層，有規(guī)則的重復(fù)結(jié)構(gòu)3. Secondary Structure: a Helix, b Sheet, Turns and Loops-螺旋 (- helix)：肽平面同一軸旋轉(zhuǎn)，螺旋一周，沿軸上升的距離

29、即螺距為0.54nm,含3.6個(gè)氨基酸殘基；兩個(gè)氨基酸之間的距離為0.15nm;肽鏈內(nèi)形成氫鍵，氫鍵的取向幾乎與軸平行，第一個(gè)氨基酸殘基的酰胺基團(tuán)的-C=O基與第四個(gè)氨基酸殘基酰胺基團(tuán)的-NH2基形成氫鍵。3. Secondary Structure: a Helix, b Sheet, Turns and Loops右手a-螺旋3. Secondary Structure: a Helix, b Sheet, Turns and LoopsFigure 2.31 Ramachandran diagram for helices. Both right-and left-handedhelic

30、es lie in regions of allowed conformations in the Ramachandrandiagram. However, essentially all a helices in proteins are right-handed.y ：-47°f ：-57 °3. Secondary Structure: a Helix, b Sheet, Turns and Loops球-棒模型綢帶結(jié)構(gòu)圓柱結(jié)構(gòu)3. Secondary Structure: a Helix, b Sheet, Turns and LoopsFigure 2.29 S

31、tructure of the a helix. A ribbon depiction with the a-carbon atoms and side chains (green) shown.3. Secondary Structure: a Helix, b Sheet, Turns and LoopsFigure 2.29 Structure of the a helix. A side view of a ball-and- stick version depicts the hydrogen bonds (dashed lines) between NH and CO groups

32、.3. Secondary Structure: a Helix, b Sheet, Turns and Loops（C）從末端向螺旋骨架內(nèi)部觀測的結(jié)構(gòu)圖，其中側(cè)鏈（綠色）向螺旋外凸出。（D）圖C的空間填充模型，表明螺旋內(nèi)部核堆積緊密。3. Secondary Structure: a Helix, b Sheet, Turns and Loops富含-螺旋的蛋白質(zhì)：鐵儲(chǔ)存蛋白由24個(gè)蛋白，是生物用于儲(chǔ)存鐵離子的主要蛋白。鐵儲(chǔ)存蛋白Figure 2.33 A largely a-helical protein.Ferritin, an iron-storage protein, is buil

33、t from a bundle of a helices.3. Secondary Structure: a Helix, b Sheet, Turns and Loops-片層（ - sheet）：b-折疊是由兩條或多條幾乎完全伸展的肽鏈平行排列，通過鏈間的氫鍵交聯(lián)而形成；肽鏈的主鏈呈鋸齒樁折疊構(gòu)象；a-碳原子總是處于折疊的角上，氨基酸的R基團(tuán)處于折疊的棱角上并與棱角垂直；3. Secondary Structure: a Helix, b Sheet, Turns and Loopsb-折疊有兩種類型：平行式：即所有肽鏈的N-端都在同一邊反平行式：即相鄰兩條肽鏈的方向相反綢帶結(jié)構(gòu)3. Se

34、condary Structure: a Helix, b Sheet, Turns and Loops相鄰的b -鏈排列方向相反。一條鏈某一氨基酸殘基的C=O和NH2基團(tuán)與配對鏈單個(gè)相鄰氨基酸的NH和C=O基團(tuán)分別形成氫鍵An anti parallel b sheet. Adjacent b strands run in opposite directions. Hydrogen bonds between NH and CO groups connect each amino acid to a single amino acid on an adjacentstrand, stabil

35、izing the structure3. Secondary Structure: a Helix, b Sheet, Turns and Loops相鄰b -鏈方向相同。一條鏈某一氨基酸殘基的C=O和NH2基團(tuán)分別與配對鏈一個(gè)氨基酸的NH2和該氨基酸下游第二位氨基酸殘基的C=O基團(tuán)形成氫鍵A parallel b sheet. Adjacent b strands run in the same direction. Hydrogen bonds connect each amino acid on one strand with two different amino acids on

36、the adjacent strand.3. Secondary Structure: a Helix, b Sheet, Turns and Loops平行式：反平行式：Figure 2.34 Ramachandran diagram for b strands. The red area shows the sterically allowed conformations of extended, b- strand-like structuresy ：+135°f ：-139°y ：+113°f ：-119°3. Secondary Structu

37、re: a Helix, b Sheet, Turns and LoopsFigure 2.38 Structure of a mixed B sheet.3. Secondary Structure: a Helix, b Sheet, Turns and Loops球-棒結(jié)構(gòu)模型片層結(jié)構(gòu)Figure 2.39 A twisted b sheet. (A) A ball and-stick m.(B) Aschematic m. (C) The schematic view rotated by 90 degrees toillustrate the twist more clearly.3

38、. Secondary Structure: a Helix, b Sheet, Turns and Loops富含-片層的蛋白質(zhì)：在長鏈脂肪駿的攝取、轉(zhuǎn)運(yùn)及代謝調(diào)節(jié)中發(fā)揮著重要作用脂肪酸結(jié)合蛋白Figure 2.40 A protein rich in b sheets. The structure of afatty acid-binding protein.3. Secondary Structure: a Helix, b Sheet, Turns and Loops蛋白質(zhì)結(jié)構(gòu)：-轉(zhuǎn)角和無規(guī)卷曲，非重復(fù)性結(jié)構(gòu)改變多肽鏈的3. Secondary Structure: a Helix,

39、b Sheet, Turns and Loops-轉(zhuǎn)角（ - turn）：由四個(gè)氨基酸殘基組成，Gly、Pro殘基較多彎曲處的第一個(gè)氨基酸殘基的 -C=O 和第四個(gè)殘基的 N-H 之間形成氫鍵，形成一個(gè)的環(huán)狀結(jié)構(gòu)。蛋白質(zhì)倒轉(zhuǎn)肽鏈方向3. Secondary Structure: a Helix, b Sheet, Turns and Loops無規(guī)卷曲（ random coil）：又稱卷曲，是沒有一定規(guī)律的松散肽鏈結(jié)構(gòu)柔性強(qiáng)，酶功能部位經(jīng)常處于這種構(gòu)象區(qū)域3. Secondary Structure: a Helix, b Sheet, Turns and Loops抗體蛋白表面有環(huán)狀結(jié)構(gòu)的區(qū)

40、域Figure 2.42 Loops on a protein surface.A part of an anti-body molecule has surface loops (shown in red) that mediateinteractions with other molecules.4. Tertiary Structure: Water-Soluble Proteins Fold into Compact Structures with Nonpolar Cores蛋白質(zhì)的三級結(jié)構(gòu)(Tertiary Structure)是指在結(jié)構(gòu)基礎(chǔ)上，肽鏈的不同區(qū)段的側(cè)鏈基團(tuán)相互作用在空

41、間進(jìn)一步盤繞、折疊形成的三維結(jié)構(gòu)。主鏈和側(cè)鏈構(gòu)象在內(nèi)的特征維系這種特定結(jié)構(gòu)的要有氫鍵、疏水鍵、離子鍵和范等。尤其是疏水鍵，在蛋白質(zhì)三級結(jié)構(gòu)中起著重要作用。可溶性蛋白折疊成結(jié)構(gòu)緊密的疏水核4. Tertiary Structure: Water-Soluble Proteins Fold into Compact Structures with Nonpolar Cores在側(cè)鏈?zhǔn)杷I作用下不規(guī)則折疊4. Tertiary Structure: Water-Soluble Proteins Fold into Compact Structures with Nonpolar Cores模體(mo

42、tif，超結(jié)構(gòu))：數(shù)個(gè)至數(shù)十個(gè)AA組成的具有自身相對構(gòu)象和功能的小區(qū)域，模體可結(jié)構(gòu)域，也可。結(jié)構(gòu)的組合結(jié)構(gòu)形式有3種：，超細(xì)胞色素C的結(jié)構(gòu)細(xì)胞核抗原的結(jié)構(gòu)纖溶酶原的結(jié)構(gòu)4. Tertiary Structure: Water-Soluble Proteins Fold into Compact Structures with Nonpolar Cores結(jié)構(gòu)域(domain) ：在結(jié)構(gòu)或超結(jié)構(gòu)的基礎(chǔ)上，多肽鏈可形成在三級結(jié)構(gòu)層次上的局部折疊區(qū)，稱為結(jié)構(gòu)域。從30氨基酸殘基到400氨基酸殘基不等。免疫細(xì)胞表面蛋白CD4的胞外部分Figure 2.52Protein domains. The ce

43、ll-surface protein CD4consists of four similar domains.4. Tertiary Structure: Water-Soluble Proteins Fold into Compact Structures with Nonpolar Cores肌紅蛋白的三維結(jié)構(gòu)Three-dimensional structure of myoglobin. (A) A ribbon diagram showsthat the protein consists largely of a-helices. (B) A space-filling min th

44、esame orientation shows how tightly packed the folded protein is. Notice that the heme group is nestled into a crevice in the compact protein with only an edge exposed. One helix is blue to allow comparison of the two structuraldepictions.4. Tertiary Structure: Water-Soluble Proteins Fold into Compa

45、ct Structures with Nonpolar Cores血紅蛋白的氨基酸分布Distribution of amino acids in myoglobin. (A) A space-filling mofmyoglobin with hydrophobic amino acids shown in yellow, charged amino acids in blue, and others in white. Notice that the surface has many charged amino acids, as well as some hydrophobic amin

46、o acids. (B) In this cross-sectional view notice that mostly hydrophobic amino acids are found on the inside of the structure, whereas the charged amino acids are foundon the protein surface.4. Tertiary Structure: Water-Soluble Proteins Fold into Compact Structures with Nonpolar Cores外膜蛋白“內(nèi)外翻轉(zhuǎn)”肽鏈中所有

47、原子在三維空間的排布位置，間作用力的綜合結(jié)果"Inside out" amino acid distribution in porin. The outside of porin (which contacts hydrophobic groups in membranes) is covered largely with hydrophobic residues, whereas the center includes a water-filled channel lined with charged and polar amino acids.5. Quaternary

48、 Structure: Multisubunit蛋白質(zhì)的四級結(jié)構(gòu)(Quaternary Structure)是指由多條各自具有完整三級結(jié)構(gòu)的肽鏈通過非共價(jià)鍵連接起來的結(jié)構(gòu)形式；肽鏈通常稱為或亞Subunit各間的結(jié)合要是氫鍵和離子鍵5. Quaternary Structure: MultisubunitQuaternary structure：多蛋白內(nèi)多肽鏈之間的相互作用l-噬菌體的cro蛋白是DNA結(jié)合蛋白，兩個(gè)相同的二聚體Figure 2.53 The Cro protein of bacteriophage l is a dimer of identical subunits.5. Q

49、uaternary Structure: Multisubunit人血紅蛋白a2b2四聚體（紅色）是完全相同的，兩個(gè)ba2b2四聚體中兩個(gè)a色）也完全相同。（黃The a2b2 tetramer of human hemoglobin.6. The Amino Acid Sequence Determines Its Three-Dimensional Structure蛋白質(zhì)折疊是一種高度協(xié)調(diào)的過程，氨基酸序列決定三維結(jié)構(gòu)6. The Amino Acid Sequence Determines Its Three-Dimensional Structure1） 蛋白質(zhì)的構(gòu)象是其正常生理功能

50、的基礎(chǔ)常見的蛋白質(zhì)變性劑：尿素鹽酸胍-巰基乙醇破壞二硫鍵和非共價(jià)作用：破壞蛋白質(zhì)的折疊The disulfide bonds can be cleaved reversibly by b-mercaptoethanolAgents for disrupting noncovalent bonds: Urea and Guanidinium chloride 6. The Amino Acid Sequence Determines Its Three-Dimensional Structure-巰基乙醇將二硫鍵還原為游離半胱氨酸Figure 2.57 Role of b-mercaptoeth

51、anol in reducing disulfide bonds. Note that, as the disulfides are reduced, the b-mercap- toethanol is oxidized and forms dimers.6. The Amino Acid Sequence Determines Its Three-Dimensional Structure蛋白質(zhì)變性：當(dāng)一個(gè)蛋白質(zhì)處于螺旋松散沒有正常生物活性狀態(tài)時(shí)，我們稱這個(gè)蛋白質(zhì)已經(jīng)變性（denatured)。核糖核酸酶Figure 2.58 Reduction and denaturation of r

52、ibonuclease.6. The Amino Acid Sequence Determines Its Three-Dimensional Structure折疊狀態(tài)轉(zhuǎn)化成非折疊狀態(tài)。增加變性劑濃度，大多數(shù)蛋白質(zhì)從折疊狀態(tài)變成非折疊狀態(tài)的轉(zhuǎn)變過程很急。Figure 2.63 Transition from folded to unfolded state. Most proteins show a sharp transition from the folded to the unfolded form on treatment with increasing concentrations

53、 of denaturants.6. The Amino Acid Sequence Determines Its Three-Dimensional Structure蛋白質(zhì)折疊不是隨機(jī)搜尋，而是逐步折疊正確的Figure 2.66 Proposed folding pathway of chymotrypsin inhibitor. Local regions with sufficient structural preference tend to adopt their favored structures initially (1). These structures come to

54、gether to form a nucleus with a nativelike, but still mobile, structure (4). This structure then fully condenses to form the native, more rigid structure (5).6. The Amino Acid Sequence Determines Its Three-Dimensional Structure蛋白質(zhì)復(fù)性：采用透析的除去-巰基乙醇和尿素，核糖核酸酶的活性又慢慢恢復(fù)。蛋白質(zhì)變性后不一定能夠復(fù)性Re-establishing correct di