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Welcome to this
talk on chemokines.
My name is Dr. James Pease.
I'm a reader in
at the National Heart & Lung Institute at
Imperial College London, United Kingdom.
The outline of this talk on
chemokines is in three parts.
In the first part, I'm going to
talk about chemokines themselves.
I'm going to introduce their classification,
their function and their signalling.
In the second part,
I'll talk about how microbes have corrupted
the chemokines system for their own purposes.
In the third and final part,
I'll talk about work on the therapeutic blockade
of chemokine receptors in various diseases.
Let's start off by introducing chemokines and talking
about their classification, function and signalling.
The term chemokine
is a portmanteau.
It comes from the phrase
and defines cytokines that
drive the chemotaxis of cells.
Chemokines are small
typically around 8-10
kDa in molecular weight
and they adopt a
as shown here in this slide.
It's notable for the presence
of a 'greek-key' motif,
which is three anti-parallel
β pleated sheets
and the C-terminal α helix.
The structure of a chemokine is
underpinned by two disulfide bonds,
and they're typically
secreted as mature peptides
following the removal or excision
of a short signal peptide.
The family of 40 or so
chemokines in the human
can be conveniently subdivided
into four major classes,
and that's based on their arrangement
of N-terminal cysteine residues.
The majority of chemokines
fall into the families
known as the CC and
the CXC families.
CC chemokines concern an N-terminus
with two adjacent cysteine residues,
whereas the CXC chemokines have a single amino
acid interspersed between the cysteines.
There are also a couple of
minor chemokine families.
The CX_3C family contains three amino
acids between these N-terminal cysteines.
Whilst the C chemokines have a single
cysteine residue in their N-terminus.
Chemokines are predominately
quite basic molecules,
and they have several conserved
lysine and arginine residues,
notably in the C-terminus.
The primary function of chemokines
is shown on this slide here.
They drive the
chemotaxis of cells.
That can be defined as the directional migration
of a cell towards a chemical stimulus.