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5.2 펩티드 -표5.3 중요한작용 -페니실아민 구조(그림5.14) 5.3 단백질 *다양한기능 -촉매작용 -구조 -운동 -방어능력 -조절작용 -운반작용 -저장 -스트레스반응 *다양한 단백질 -섬유상, 구상단백질 -복합단백질:보결분자단(비단백질성분)결합, -아포단백질, 홀로단백질 -당단백질, 지질단백질 -금속단백질, 인산단백질, 혈색소단백질 Section 5.2: Peptides Less structurally complex than larger proteins, peptides still have biologically important functions Glutathione is a tripeptide found in most all organisms and is involved in protein and DNA synthesis, toxic substance metabolism, and amino acid transport Vasopressin is an antidiuretic hormone that regulates water balance, appetite, and body temperature Oxytocin is a peptide that aids in uterine contraction and lactation From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.2: Peptides From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Of all the molecules in a living organism, proteins have the most diverse set of functions: Catalysis (enzymes) Structure (cell and organismal) Movement (amoeboid movement) From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Defense (antibodies) Regulation (insulin is a peptide hormone) Transport (membrane transporters) Storage (ovalbumin in bird eggs) Stress Response (heat shock proteins) From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Due to recent research, numerous multifunction proteins have been identified Proteins are categorized into families based on sequence and three-dimensional shape Superfamilies are more distantly related proteins (e.g., hemoglobin and myoglobin to neuroglobin) Proteins are also classified by shape: globular and fibrous Proteins can be classified by composition: simple (contain only amino acids) or conjugated Conjugated proteins have a protein and nonprotein component (i.e., lipoprotein or glycoprotein) From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press (1)단백질의 구조 -단백질구조(그림5.15) -1,2,3,4차구조 *1차구조 -아미노산서열 -헤모글로빈 사슬서열(그림5.16) -상동성: 시토크롬 C *1차구조, 진화 그리고 분자병 -시토크롬 C -헤모글로빈, 분자병 *2차구조 -알파-나선, 베타-병풍 -phi, psi결합각도 -그림5.17-18 -알파나선:수소결합, 3.6개/회전, 0.54nm/회전, 글루탐산, 트립토판(거대한 R기): 알파나선구조를 못함 -베타병풍(그림5.19):인접된 사슬의 작용기 사이에 수소결합 평행과 역평행구조 -두 이차구조의 조합으로 구성: 초2차구조(그림5.20) Section 5.3: Proteins Protein Structure Proteins are extraordinarily complex; therefore, simpler images highlighting specific features are useful Space-filling and ribbon models Levels of protein structure are primary, secondary, tertiary, and quaternary Figure 5.15 The Enzyme Adenylate Kinase From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Figure 5.16 Segments of b-chain in HbA and HbS Primary Structure is the specific amino acid sequence of a protein Homologous proteins share a similar sequence and arose from the same ancestor gene When comparing amino acid sequences of a protein between species, those that are identical are invariant and presumed to be essential for function From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Primary Structure, Evolution, and Molecular Diseases Due to evolutionary processes over time, the amino acid sequence of a protein can change due to alterations in DNA sequences called mutations Many mutations lead to no change in protein function Some sequence positions are less stringent (variable) because they perform nonspecific functions Some changes are said to be conservative, because it is a change to a chemically similar amino acid From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Figure 5.16 Segments of b-chain in HbA and HbS Primary Structure, Evolution, and Molecular Diseases Continued Mutations can be deleterious, leading to molecular diseases Sickle cell anemia is caused by a substitution of valine for a glutamic acid in b-globin subunit of hemoglobin Valine is hydrophobic, unlike the charged glutamic acid From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Primary Structure, Evolution, and Molecular Diseases Continued The substitution for hydrophobic valine HbS: molecules aggregate to form sickle-shaped cells These cells have low oxygenbinding capacity and are susceptible to hemolysis Figure 5.17 Sickle Cell Hemoglobin From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Secondary Structure: Polypeptide secondary structure has a variety of repeating structures Most common include the a-helix and bpleated sheet Both structures are stabilized by hydrogen bonding between the carbonyl and the N-H groups of the polypeptide’s backbone Figure 5.18 The a-Helix From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins The a-helix is a rigid, rod-like structure formed by a right-handed helical turn a-Helix is stabilized by N-H hydrogen bonding with a carbonyl four amino acids away Glycine and proline do not foster a-helical formation Figure 5.18 The a-Helix From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Figure 5.19 b-Pleated Sheet The b-pleated sheets form when two or more polypeptide chain segments line up, side by side From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Each b strand is fully extended and stabilized by hydrogen bonding between N-H and carbonyl groups of adjacent strands Parallel sheets are much less stable than antiparallel sheets Figure 5.19 b-Pleated Sheet From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Figure 5.20 Selected Supersecondary Structures Many proteins form supersecondary structures (motifs) with patterns of a-helix and b-sheet structures (a) bab unit (b) b-meander (c) aa unit (d) b-barrel (e) Greek key From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Steric Constraints on phi & psi -G. N. Ramachandran was the first to demonstrate the convenience of plotting phi,psi combinations from known protein structures - The sterically favorable combinations are the basis for preferred secondary structures Figure 6.4 A Ramachandran diagram showing the sterically reasonable values of the angles f and y. The shaded regions indicate particularly favorable values of these angles. Dots in purple indicate actual angles measured for 1000 residues (excluding glycine, for which a wider range of angles is permitted) in eight proteins. The lines running across the diagram (numbered +5 through 2 and -5 through -3) signify the number of amino acid residues per turn of the helix; “+” means right-handed helices; “-” means left-handed helices. (After Richardson, J. S., 1981, Advances in Protein Chemistry 34:167–339.) *3차구조 -구상구조: 접힘현상 -3차구조의 특징: 147페이지 (그림5.21=도메인) -3차구조의 안정화: 소수성상호작용, 정전기적인력, 수소결합, 공유결합(번역후 수식)(그림5.23), 수화(그림5.24) *4차구조 -다중소단위 단백질 -단위체, 이합체, 사합체 -공유교차결합은 다중체를 안정화시킴: 이황화결합, 면역글로불린 G(그림5.25) 결합조직단백질의 데스모신, 리시노노스루신 (엘라스틴에서)(그림5.26) -다른자리입체성: 다른자리 전이유도 리갠드를 효과물질(effector)혹은 조절물질(modulator) *단백질역학: 구조의 안정과 유연성, 단백질-리갠드상호작용 *단백질구조의 상실 -변성 -bovine pancreatic ribonuclease, β-mercaptoethanol과 8M urea로 처리(그림5.28) -단백질 변성의 조건 –page155-157: 염! Section 5.3: Proteins Tertiary Structure refers to unique threedimensional structures formed by globular proteins Also prosthetic groups Protein folding is the process by which a nascent molecule acquires a highly organized structure Information for folding is contained within the amino acid sequence Interactions of the side chains are stabilized by electrostatic forces From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Tertiary structure has several important features 1. Many polypeptides fold in a way to bring distant amino acids into close proximity 2. Globular proteins are compact because of efficient packing From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins 3. Large globular proteins (200+ amino acids) often contain several domains Domains are structurally independent segments that have specific functions Core structural element of a domain is called a fold Figure 5.21 Selected Domains Found in Large Numbers of Proteins From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Figure 5.21 Selected Domains Found in Large Numbers of Proteins From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Figure 5.21 Selected Domains Found in Large Numbers of Proteins From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Figure 5.22 Fibronectin Structure 4. A number of proteins called mosaic or modular proteins consist of repeated domains Fibronectin has three repeated domains (F1, F2, and F3) Domain modules are coded for by genetic sequences created by gene duplications From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Figure 5.23 Interactions That Maintain Tertiary Structure Interactions that stabilize tertiary structure are hydrophobic interactions, electrostatic interactions (salt bridges), hydrogen bonds, covalent bonds, and hydration From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Figure 5.25 Structure of Immunoglobulin G Quaternary structure: a protein that is composed of several polypeptide chains (subunits) Multisubunit proteins may be composed, at least in part, of identical subunits and are referred to as oligomers (composed of protomers) From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Reasons for common occurrence of multisubunit proteins: 1. Synthesis of subunits may be more efficient 2. In supramolecular complexes replacement of worn-out components can be handled more effectively 3. Biological function may be regulated by complex interactions of multiple subunits Figure 5.25 Structure of Immunoglobulin G From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Polypeptide subunits held together with noncovalent interactions Covalent interactions like disulfide bridges (immunoglobulins) are less common Other covalent interactions include desmosine and lysinonorleucine linkages Figure 5.26 Desmosine and Lysinonorleucine linkages From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Interactions between subunits are often affected by ligand binding An example of this is allostery, which controls protein function by ligand binding Can change protein conformation and function (allosteric transition) Ligands triggering these transitions are effectors and modulators From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press Section 5.3: Proteins Figure 5.27 Disordered Protein Binding Unstructured proteins: Some proteins are partially or completely unstructured Unstructured proteins referred to as intrinsically unstructured proteins (IUPs) or natively unfolded proteins Often these proteins are involved in searching out binding partners (i.e., KID domain of CREB) From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press