大一下課件梅第三章en

1、12(I) Secondary Structure ： The local spatial arrangement of amino acid residues that are nearby in the sequence, that is, the relative positions of backbone atoms of a certain peptide segment. The side chains are not considered. Forms: helix, pleated sheet, turn, helix, random coilMajor Bond：Hydrog

2、en bond I. Conformation of Protein3Right-handed helix3.6 amino acid residues per turn of helixThe pitch of the helix is 0.54nm, diameter is 0.23nmThe N-H of every peptide bond is hydrogen-bonded to the C=O of neighboring peptide bond located four peptide bonds away in the same chain., including 13 a

3、toms ,so also known as 3.613 helix.All the main chain C=O and NH are hydrogen bonded.Linus Pauling 1. - helix(1)4The alpha helix is a coiled secondary structure due to a hydrogen bond every fourth amino acid56Direction of hydrogen bonds are parallel to the vertical axis of helix.The stability of an

4、-helix arises primarily from hydrogen bonds.The side chains are on the outside of the helix, not directly participate in the formation of helix .-helix is the most stable secondary conformation1. -helix(2)：78Adjacent peptide unit form a zigzag or pleated pattern, the intersection angle is 110。.-Shee

5、ts are stabilized by hydrogen bonding between polypeptide strands. The direction of hydrogen bonds are vertical to the peptide strands. Adjacent chains in a b sheet can run in opposite directions (antiparallel b sheet) or in the same direction (parallel b sheet).The side chains of adjacent amino aci

6、ds point in opposite directions2.-pleated sheet structure 91011Peptide chain arises a tight 180turn . A-turn involves four amino acid residues, the first residues is hydrogen bonded to the fourth .Proline is often present in-turnOften lie on the globulin surface and serve key biologic role. 3.-turn1

7、213Left-handed helix，4.4 amino acid residues per turn.Hydrogen bonds stabilize the -helix，every hydrogen bond across 18 atoms ,so also named as 4.418 helix.Often found in collagen. Triple left-handed helixes twist to form right-handed super helix and turn to collagenous fibers.4.-helix1415uGeneral n

8、ame of a series of unordered conformation in protein.u Important structural and functional segments of protein.5. Random Coil166.Supersecondary Structure of Cytochrome C of PCNAof plasminogen17Motif in Calcium-binding Protein Zinc Finger Side chains can disrupt or induce the formation of secondary s

9、tructure Shape: Pro having a rigid ring (helix disrupter) Size: helix and -sheet needs AAs of small side chain. Leu, Ile, Trp, and Asn, having bulky sides, hard to form helix and -sheet ) Charge: Too many charged AAs in a short region of one peptide is hard to form helix.1819*Definition:The entire t

10、hree-dimensional conformation of a polypeptide chain. It refers to the spatial arrangement of amino acid residues that are far apart in the sequence and to the pattern of disulfide bonds.It indicates, in three-dimensional space, how secondary structural assemble to form domains and how these domains

11、 relate spatially to one another.(II) Tertiary Structure 20uSingle or several super secondary structure units gather and fold independently into a compact, stable structure, termed domain.uDomain is the function element of protein. The different domains of a protein are often associated with differe

12、nt functions. uDomain is the partial folding region at the level of tertiary structure. Motif is its subunit.uEvery domain is encoded by one exon.Domain（結(jié)構(gòu)域）（結(jié)構(gòu)域）21NADHPyruvateLactate Dehydrogenase N terminalC terminal EGF ReceptorIntracellular protein kinase domain is regulated via the binding of t

13、he peptide hormone EGF to its extracellular domain.2223*Features： To the single peptide protein, tertiary structure is the highest level of structure. Form hydrophilic surface and hydrophobic inner core.*Major Bond：Hydrophobic Interaction24Myoglobin(肌紅蛋白肌紅蛋白)25Quaternary structure defines the polype

14、ptide composition of a protein for an oligomeric protein, and the spatial relationships between its subunits.Subunit（亞基）（亞基） Each polypeptide chain in such a protein is called a subunit. Subunit is inactive when it exists alone.(III) Quaternary Structure 26Features:Quarternary structure arises when

15、two or more polypeptides join to form a proteinSubunit is inactive when it exists on its own.Subunits are linked by secondary bonds（H-bonds, ionic interactions, and hydrophobic interactions）If the peptide chains are linked by covalent bonds (disulfide bond) ，it is not belong to quaternary structure.

16、Polypeptide chains can be in dimer, trimer ., as well as homo- or hetero-form. For example, hemoglobin is composed of 4 polypeptide chainsLink to video27NH3 COO 2 NH3 COO 2 COO NH3 1COO NH3 1Asp HisArg Asp LysLys Asp ArgHis Asp94 146141 126 4040 126 141146 94Ionic Forces in Hemoglobin282930 Primary

17、Structure：Peptide bond、Disulfide bond Secondary Structure：Hydrogen bond Tertiary Structure：Hydrophobic interaction Quaternary Structure：Ioni c bond (IV)Non-covalent Bonds stabilize Protein Structure31 Hydrogen bondA hydrogen atom is shared by two other atoms. H-donor: the atom to which H atom is mor

18、e tightly attached, and the other is H-acceptor. 32 Hydrophobic interactionNonpolar molecules tend to cluster together in water, that is, amino acids with nonpolar side chains cluster in the core of the protein, out of contact with water33 A charged group is able to attract another group of opposite

19、 charges. Ionic interaction34 The attraction between a pair of atoms increases as they come closer, until they are repelled by van der Waals contact distance. van der Waals force 35 Disulfide bridgeStrong covalent bonds between sulfur atoms in the amino acid cysteine36The folding of many proteins is

20、 protected by chaperonin proteins that shield out bad influences.Chaperon37Post-translational Modification3839II. Structure-Function Relationship of Proteins Sequence of DNA Amino acid sequence of proteinConformation of ProteinFunction of ProteinPrimary structure is basis, Conformation is the key fa

21、ctor.401.The alternation of key AAs in a protein will cause the loss of its biological functions Sickle cell anemia Abnormal hemoglobin, develop because of a single amino acid substitution. This is the first case of molecular disease identified in history(I) Primary Structure and Function41HbA Val-H

22、is-Leu-Thr-Pro-Glu-Glu-LysHbS Val-His-Leu-Thr-Pro-Val-Glu-Lys4243 分子病分子病 相應(yīng)蛋白質(zhì)分子的異?；蛉笔鄳?yīng)蛋白質(zhì)分子的異?；蛉笔х牋罴?xì)胞貧血鐮狀細(xì)胞貧血 血紅蛋白血紅蛋白家族性高膽固醇血癥家族性高膽固醇血癥 低密度脂蛋白受體低密度脂蛋白受體原發(fā)性痛風(fēng)病原發(fā)性痛風(fēng)病 磷酸核糖焦磷酸酶磷酸核糖焦磷酸酶白化病白化病 酪氨酸酶酪氨酸酶血友病血友病A與與B 凝血因子凝血因子與與重度聯(lián)合免疫缺陷癥重度聯(lián)合免疫缺陷癥(SCID) 腺苷脫氨酶腺苷脫氨酶苯丙酮酸尿癥苯丙酮酸尿癥 苯丙氨酸羥化酶苯丙氨酸羥化酶蠶豆病蠶豆病 6-磷酸葡萄糖脫氫酶磷

23、酸葡萄糖脫氫酶頑固性佝僂病頑固性佝僂病 25-羥維生素羥維生素D31-羥化酶羥化酶Lesch-Nyhan(自毀臉容自毀臉容) 次黃嘌呤次黃嘌呤-鳥嘌呤磷酸鳥嘌呤磷酸綜合征綜合征 核糖轉(zhuǎn)移酶核糖轉(zhuǎn)移酶 Molecular Disease分子病分子病Inherited diseases in which the manifestations are due to alterations in protein primary structure and function . The AA variation is due to the gene mutation.442. Proteins havi

24、ng similar amino acid sequences demonstrate the functional similarity. *InsulinA8A9 A10A30Human ThrSerIle ThrBovineAlaSerVal AlaSwineAlaSerIle AlaOvineAlaGlyVal Ala45ACTH (促腎上腺皮質(zhì)激素促腎上腺皮質(zhì)激素)and MSH (促黑激素促黑激素) have a same peptide segment, so ACTH also has the function of promoting melanogenesis.46Cyto

25、chrome C is a protein which can be found in all a e r o b i c o r g a n i s m s . Comparison of their primary structure can help t o u n d e r s t a n d t h e evolutionary relationship between different species. Organisms which are closer in the process of species evolution will have more similar pr

26、imary structure of cytochrome C. 47(II) Spatial structure and function Proteins will experience multiple processes to become correctly folded, that is, having a correct structure. The incorrect protein structure may lead to function alternation or diseases. A particular spatial structure of a protei

27、n is strongly correlated with its specific biological functions.481.Amphipathichelix1.Amphipathichelix492Ion ChannelHydrophobic amino acidHydrophobic amino acidHydrophilic amino acidCell Membrane2.The structural properties of silk are due to beta pleated sheets.The presence of so many hydrogen bonds

28、 makes each silk fiber stronger than steel.5051An effect that arises when the binding of an effector molecule at the polymeric proteins allosteric site regulates protein activity as a result of conformational changes. 1)Only proteins which have quaternary structure possess this property. 2)Allosteri

29、c agents are small physiological molecules, such as O2、ATP3)Allosteric site is a site other than the proteins active site.4)Slightly change conformation can increase or decrease protein activity subsequently. 3. Allosteric effect（變構(gòu)效應(yīng)（變構(gòu)效應(yīng))5253The iron atom moves into the plane of the heme on oxygen

30、ation. Histidine F8 and its associated residues are pulled along with the iron atom.54The Allosteric Effect of Hemoglobins55Schematic Diagram of Allosteric Effect of Hemoglobin56573.蛋白質(zhì)構(gòu)象改變可導(dǎo)致構(gòu)象病蛋白質(zhì)構(gòu)象改變可導(dǎo)致構(gòu)象病 Protein Conformational Disorders： A class of diseases in which certain proteins fail to fol

31、d into their normal conformation and lose their normal function, thereby disrupt the function of cells, tissues and organs of the body.58 Pathogenic Mechanism：Some misfolding proteins aggregate and form anti-protease amyloidosis, and thereby cause disease. Diseases: Alzheimers disease, Parkinsons di

32、sease, prion disease, type 2 diabetes, amyloidosis59BSE is a transmissible, inheritable neurodegenerative diseases in mammals caused by prion protein (PrP,朊病毒蛋白).Normal PrP is rich in -helix，termed PrPc. PrPc is a normal constituent of brain tissue in all mammals.Abnormal PrP is rich in pleated shee

33、t, termed PrPsc.A number of PrPsc aggregate extracellularly within the central nervous system to form plaques known as amyloid, which destroy brain tissues by converting them to a spongy appearance disrupt and lead to brain damage and death.Bovine spongiform encephalopathy (BSE,瘋牛病瘋牛病) 60 NH3+ NH3+

34、NH2 NH3+ NH3+ NH2 COOH COO- COO- COOH COO- COO-Positive Ion Zwitterion Negative IonPositive Ion Zwitterion Negative Ion （pHPI)pHPI) P P PP P PIII. Physicochemical Properties of Protein(I)Ampholyte of protein1.+H+H+H+H+ +OH+OH+OH+OH612.pI of Protein： the pH at which a particular molecule carries no n

35、et electrical charge.3.The charge of protein is related to surroundings pH. pH PI negative ion pH = PI electric neutrality4. pI of most protein is 5.0, and negatively charged in body fluid (pH7.4) pI 7.4: basic proteins: protamine, histone pI 7.4: acidic proteins: pepsin 62 Serum Protein Electrophor

36、etogram_+ 2 1 63(II)Macromolecule Properties 1.Stability of Hydrophilic colloid is due to : Hydration Shell Electric Repulsion 2.Dialysis 3.UltracentrifugationMW : 10,000 1,000,000Diameter: 1100nm, in the range of colloid(III)UV absorption max：280nm（Tyr，Trp）64+Positive Charged ProteinPositive Charge

37、d ProteinNegative Charged ProteinNegative Charged Protein Protein in pI Protein in pIHydration ShellHydration Shell+Positive Charged ProteinPositive Charged ProteinNegative Charged ProteinNegative Charged ProteinUnstable ProteinUnstable ProteinacidacidbasebaseacidacidbasebaseacidacidbasebaseDehydrationDehydrationDehydrationDehydrationDehydrationDehydrationPrecipitation of ProteinPrecipitation of Protein65 (IV) Denaturation（蛋白質(zhì)的變性）（蛋白質(zhì)的變性）1.DefinitionThe process in which a protein loses its native conformation under the treatment of denaturants.(1)Denaturants：physical: heat,