Download Section 5.3: Proteins

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