Download College 5

College 4
Coordination interaction
•
•
•
•
A dipolar bond, or coordinate covalent bond, is a description of covalent
bonding between two atoms in which both electrons shared in the bond come
from the same atom.
Once such a bond has been formed, its strength and description is no different
from that of other polar covalent bonds.
They may involve metal ions. In such complexes, a molecule "donates"
its"free" pairs of electrons to an otherwise naked metal cation, that "accepts"
the electrons.
For example O2 or CO to the Fe in porphyrins.
Protein folding
Proteins fold into a unique 3-D structure with a unique biological function. Even a
mutation of one single amino acid may perturb this process in the sense that no
longer a stable structure can be formed, or if it is formed it has no, or a much
reduced, biological activity.
Folded state → minimum in energy
‘Simple’ rules:
1. Two atoms can never be in the same place.
Steric hindering is one of the major driving
forces for the formation of secondary structure
Protein folding
2. Covalent connections between different parts of the chain can be made by disulfide bridges, involving two cysteines (see fig 4.25 and 4.26).
A disulfide bridge in a protein is exceptionally stable.
When a protein is being produced by the ribosome, a certain
number of cysteine residues will be present.
Protein folding
3. Non-covalent interactions.
As a result of ionic interactions, Van der Waals forces and hydrogen bonds,
each type of protein has a particular three dimensional structure, which is
determined by the order of the amino acids in the chain.
Folded proteins
The final folded structure, or conformation, is the one in which the free energy is
minimized (this minimum may not be unique for a system with so many degrees
of freedom).
For globular, water soluble proteins this is generally a compact conformation with
a hydrophobic core and polar/charged residues (such as arginine, glutamine,
histidine etc.) exposed to the aqueous phase
Water → driving force
Folded proteins
When polar residues are
buried in the inside of a
protein they are generally
hydrogen-bonded to other
polar amino acids or to the
polypeptide backbone
Protein folding
A distribution of unfolded species slide on the same
energy surface to reach the minimal free energy
They meet at the saddle point where key residues
have formed their native like contact.
Fig 4.31 Free energy of a folding
protein plotted as a function of the
number of contacts between
residues (not all are favourable)
and the number of native contacts
(meaning contacts that also occur
in the functional protein). The
potential energy drives the system
to a conformation where a certain
number of native contacts has
been established, but the chain is
not yet folded. Note that there are
many possible pathways. Once this
point is reached, the chain folds
rapidly.
Denaturation
Protein folding in a living cell is often assisted by special proteins called molecular
chaperones. These proteins bind to partly folded polypeptide chains and help
them progress along the energetically most favorable folding pathway. Chaperones
are vital in the crowded conditions of the cytoplasm, since they prevent the
temporarily exposed hydrophobic regions in newly synthesized proteins from
associating with each other to form protein aggregates.
Structures
In vitro, X-ray
Highly
organised
‘misfolded’
structure
.Disease
Denaturation
Each protein normally folds up into a single stable
configuration. However, this conformation often
changes slightly when the protein interacts with other
proteins in the cell. It is this modulation of the shape of
proteins by its interaction with the ‘environment’ that is
often crucial to the function of the protein.
Membranes
All cells are enclosed in a plasma membrane. This container acts as a selective
barrier that enables the cell to concentrate nutrients gathered from its environment
and retain the products it has synthesized for its own use, while excreting waste
products.
Without its plasma membrane the cell could not maintain its integrity as a
coordinated chemical system.
Integral membrane proteins, like
receptors and channels, cross the
membrane. Receptors often have
specific oligosaccharides attached
to them that play a role in the
recognition of specific compounds
like hormones. Binding of a
hormone then leads to a
conformational change that is
sensed at the cytosolic side of the
membrane.
Transport through membranes
A multitude of
compounds must be
transported into and
out of the cell via the
plasma membrane,
into and out of the
nucleus, mitchondria,
chloroplasts, the
golgi apparatus etc,
including synthesized
proteins!!!
Safety valves
MscL - Structure
Periplasmic side
Transmembrane proteine
Channel proteine forms a large
non-selective ‘safety valve’ to
protect the cell from lysis by
osmotic downshocks
Abundance: Plants, bacteria,
fungi, cardiovascular regulation
in animals (eg. kidneys)
Importance: Highly convenient
molecular system for studies of
elemental principles of
mechanotransduction
Cytoplasmic side
Tb-MscL – ‘closed’ (relaxed) form
Crystal structure: 3.5Å resolution
Crystal Structure: Chang et al Science, 282 (1998), 2220.
Postulated helical structure of S1, also: Sukharev et al., Biophys. J., 81 (2001), 917.
Structure of the
mechanosensitive
sensitive channel
MscL. The channel
opens in response to
pressure and
functions as a safety
valve to protect the
cell from lysis by
osmotic pressure.
Cells & membranes
• Nucleus: Genome management
• Mitochondria & chloroplasts: Energy generation
• EP & Golgi complex: protein synthesis and modification
Ion pumps using ATP
3 Na+
[Na+]=140 mM
[K+]=5 mM
2 K+
[Na+]=10 mM
70 mV
[K+]=100 mM
1 ATP
Fig 4.46 The ATP-driven K+-Na+ exchanger. Na+ and K+ are exchanged and
transported across the membrane against their gradients using ATP.