MONOMER, STRUKTUR DAN FUNGSI

PROTEIN
Materi matakuliah Biokimia Lanjut
Laboratorium Biokimia
Fakultas Biologi UGM
 Some basic concepts
in biology and biochemistry
The hierarchy of biological organism
From molecule to organism
The micro environment: Cell
DNA vs. chromosome

DNA

Chromosome
Central dogma: the story of life

DNA

RNA

Protein
 DNA structure

Atomic structure Double helix

 The basic unit in DNA

C T A G
From DNA to Protein

1. Transcription

2. Translation
Step1: Transcription, generation of mRNA
Step2: Translation, protein assembly
Amino acid carrier: tRNA
Peptide bond formation

Peptide Chain
 Writing the Structure of
18.3 The Peptide Bond Peptides
 Protein structure

Primary

Secondary
Tertiary

Quaternary
The bonds contribute to protein structure

1. Hydrogen bond

2. Hydrophobic interaction

3. Ionic bond

4. Disulfide bond
 Complexity of the protein world

DNA : 4 Nucleotides

Proteins : 20 amino
acids
The famous dogmas of biology, one gene one protein hypothesis is no tenable

RNA Splicing
Post-translational modifications

Phosphorylation Maturation Glycosylation

Proteome, unlike the genome, is not a fixed feature of an organism

Environmental stress
 An Overview of Protein
Structure and Function
Types of Protein Structure and Their
Interrelationships
1. Primary structure:
Amino acid sequence
Results from formation of covalent
peptide bonds between amino acids
2. Secondary structure:
Includes -helix and -sheet
Hydrogen bonding between amide
hydrogens and carbonyl oxygens of the
peptide bonds
18.5 The Secondary Structure of Proteins -Helix
 -Helices in Fibrils
Fibrous proteins are
arranged in a
18.5 The Secondary Structure of Proteins

secondary structure
of fibers or sheets
with only 1 type of
secondary structure
Repeated coiling of
helices
 -Pleated Sheet
Second most common secondary structure
appears similar to folds of fabric
All of the carbonyl O and amide H are involved
in the H bonds with the chain nearly
18.5 The Secondary Structure of Proteins

completely extended
Two possible orientations
Parallel if the N-termini are head-to-head
Antiparallel if the N-terminus of one chain is aligned
with the C-terminus of the other
 Types of Protein Structure
and Their Interrelationships
.8 An Overview of Protein Structure and Function

3. Tertiary structure:
Overall folding of the entire polypeptide chain
Interactions between different amino acid side
chains
4. Quaternary structure:
Concerned with topological, spatial
arrangement of two or more polypeptide
chains
Involves both disulfide bridges and
noncovalent interactions
 Hemoglobin Structure
Demonstrating the Four Levels
of Protein Structure
18.7 The Quaternary Structure of Proteins
 Interactions Involved in Tertiary
Structure
18.6 The Tertiary Structure of Proteins
Protein Structure
 Domains
A domain is a basic structural unit
of a protein structure distinct
from those that make up the
conformations
Part of protein that can fold into a
stable structure independently
Different domains can impart
different functions to proteins
Proteins can have one to many
domains depending on protein size
Domains
 Protein Functions Follow
Shape
Fibrous proteins:
8.8 An Overview of Protein Structure and Function

Mechanical strength
Structural components
Movement
Globular proteins:
Transport
Regulatory
Enzymes
 Important Peptides and Protein Hormones
Name Origin Action
Adrenocorticotropichormone(ACTH) Pituitary Stimulatesproductionofadrenal

AngiotensinII BloodPlasma Causebloodvesselstoconstrict

Folliclestimulatinghormone(FSH) Pituitary Stimulatesspermproductionand
foliclematuration
Gastrin Stomach Stimulatesstomachtosecreteacid

Glucagon Pancreas Stimulatesglycogenmetabolismin

liver
HumanGrowthHormone(HGH) Pituitary Generaleffect:bonegrowth
Insulin Pancreas Controlsmetabolismof
carbohydrates
Oxytocin Pituitary Stimulatescontractionofuterus
andothersmoothmuscles

Prolactin Pituitary Stimulateslactation

Somatostatin Hypothalamus InhibitsproductionofHGH
Vasopressin Pituitary Decreasesvolumeofurineexcreted
Proteins are the molecule tools for most cellular
functions
 Conjugated Proteins
Class Prosthetic Group Example
Nucleoprotein Nucleic acids Viruses

Lipoprotein Lipids Serum lipoproteins

Glycoprotein Carbohydrates Mucin in saliva

Phosphoprotein Phosphate groups Casein in milk

Hemoprotein Heme Hemoglobin,

cytochormes
Metalloprotein Iron, zinc Ferritin, hemoglobin
 Introduction to proteomics

www.bio.fju.edu.tw/lab/ChenHM/proteomics/ch1.ppt
 Proteomics
Proteomics is the large-scale study of proteins,
particularly their structures and functions

Initial goal was to rapidly identify all

the proteins expressed by a cell or
tissue a goal that has yet to be
achieved for any species!
There are more molecular genetic
ways to study proteins and more
biochemical ways
 Only DNA sequence is not enough

Structure
Those are what we need
Regulation to know about proteins
Information

Computers cannot determine which of

these 3 roles DNA play solely based on
sequence (although we would all like to
believe they can)
 1 gene = 1protein?

1 gene is no longer equal to one protein

The definition of a gene is debatable..(ORF,

promoter, pseudogene, gene product, etc)

1 gene = how many proteins? (never known)

Why Proteomics?
 Differential protein expression

DNA RNA Protein

Transcription Translation

x1 x4

Scenario 1: can be analyzed by microarray technology

Stimulus
DNA RNA Protein
Transcription Translation

x3

Scenario 2: can be solved by proteomics technology

Stimulus
DNA RNA Protein
Transcription Translation

x3
Co- and Post-translational modification

Co-translational modified Post-translational modified

 What proteomics can answer

Protein identification
Protein Expression Studies
Protein Function
Protein Post-Translational Modification
Protein Localization and
Compartmentalization
Protein-Protein Interactions
Process for protein isolation
 General classification for Proteomics

Protein Expression comparison

(beginning)
Quantitative study of protein expression between
samples that differ by some variable
Structural Proteomics (simulation)
Goal is to map out the 3-D structure of proteins
and protein complexes
Functional Proteomics (everything)
To study protein-protein interaction, 3-D
structures, cellular localization and PTMS in order
to understand the physiological function of the
whole set of proteome.
Two most applied technologies:

1. 2-D electrophoresis:
separation of complex protein mixtures

2. Mass spectrometry:
Identification and structure analysis
2D gel electrophoresis
MS analysis
Protein microarrays