General Index
Proteins: Introduction
Introduction
Proteins are molecules that can reach an enormous degree of structural complexity. However, we know now that protein
structure presents regularities that make their systematic structural study easier. In this introduction we'll see some general aspects of
protein structure.
The simplest concept about protein structure is that of a Linear Polymer of Aminoacids. By Linear we
understand that aminoacids are placed along a single, non-branched chain; with a beginning (that we assign by convention to the N-terminus)
and an end (that is the C-terminus). The union between residues takes place through peptide bonds.
To illustrate these concepts we'll look at the structure of Ubiquitin:
It is a small protein (76 residues) involved in intracellular proteolysis.
The protein appears in a ball-and-stick display. The atom colors correspond to the Corey-Pauling-Kultun (CPK) pattern.
Note that, in general, in protein modeling hydrogen atoms are not represented. Given the enormous number of atoms in a protein (even when small, as is the case)
this representation is somewhat confusing.
We can restrict the display to the continuum ...-NCCNCCNCC-... (the Backbone) of the protein, suppressing the display of side chains:
We see a coil with two ends: the N-terminus and the C-terminus. to distinguish them, we use the command color group:
In this rendering, the backbone appears coloured in such a way that the portion closest to the N-terminus appears in blue, while the C-terminal portion appears in red, with the intermediate colours (blue-cyan-green-yellow-orange-red) indicate the relative proximity to each of the termini. The aminoacids occupying the termini are: Methionine
We can see the side chains of the aminoacids.
The 3D structure of a portein is not random. The molecules of ubiquitin have always the same form. 3D
structure is mainly maintained by weak interactions (hydrophobic effect, hydrogen bonds, salt bridges, etc.).
the Hydrophobic Effect is very important in maintaining the structure of a protein. To see this
effect, we first select the polar residues in the protein:
The hydrophobic effect makes that a protein can be compared to a Micelle, with a hydrophobic
interior and a polar exterior, in contact with the solvent (water).
Other weak interactions that determine the protein structure are the Hydrogen Bonds. In proteins
we see many of these bonds, either between peptide groups (-CO-, -NH-) of the backbone or between donor and acceptor groups
of the side chains. To see the hydrogen bonds, we colour in green the protein and in yellow the hydrogen bonds:
Many other bonds, covalent or non-covalent, are relevant in maintaining the 3D structure of a protein.
We'll study them in other modules.
This initial concept of protein structure is very restricted. First, ubiquitin is a very small protein;
but many other factors add to the complexity of a protein. We'll see now some of them.
Index
Conjugated Proteins
There are many proteins in which not all the structure is polypeptidic, but also present different
molecular groups, called Prosthetic Groups, with well defined functions. Proteins having prosthetic groups are
called Conjugated Proteins, to be distinguished from Simple Proteins in which the whole structure is
polypeptidic. To illustrate this concept, we'll study a small conjugated protein, Cytochrome c:
Cytochrome c is a small protein (104 aminoacids) than functions as an electron carrier between the
mitochondrial complexes III and IV.
Part of this structure is a prosthetic group formed by a Heme B, that is, a protoporphyrin IX
and a coordinated iron ion:
Index
Metal Atoms
Very often proteins are associated to Metal atoms or ions, through coordinate bonds.
That is the case of Rubredoxin, also a small protein:
It is also involved in electron transport, forming part of the so-called ferredoxins (Iron-sulfur proteins,
Non-Heme Iron proteins, NHI).
Rubredoxin presents an iron ion:
Index
Oligomeric Proteins
Ubiquitin, Cytochrome c and Rubredoxin are small proteins, with only one polypeptide chain. They are
called Monomeric Proteins. However, many proteins are formed from more than one polypeptide chain, this being more
rule than exception. They are Oligomeric Proteins, formed by subunits, either identical or different. Of
these proteins we say that possess Quaternary structure (see below).
As an example, we present the structure of Concanavallin A:
Concanavallin A is a lectin. Lectins are proteins, generally from plants that can specifically
bind mono- or oligosaccharides in the cell surface receptors, causing specific effects in the cell. In this case,
Concanavallin A induces T-lymphocyte proliferation upon interaction with a mannopyranoside.
Concanavallin A is composed by four identical subunits (Homotetramer). The four subunits are: Subunit A,
Let's restrict the view to subunit A:
Another oligomeric protein, even more complex than concavallin A, is the enzyme Aspartate transcarbamylase:
it is a regulatory enzyme, which catalyzes the key step in pyrimidine biosynthesis.
The molecule is a dodecamer:
Index
Visual display of protein structures
The high number of atoms in a protein does not allow to easily represent its structure in space. For that
reason we use specific forms of representation, in which individual atoms are not represented, but only the continuum
-NCCNCCNCC-... as a ribbon in which the different secondary structures are superimposed. In the same way, there are
color codes that help us in interpreting the structure.
To illustrate the different display forms, let's see the structure of Cytochrome P450 CAM
(3cpp in the Protein Data Bank code:
The default display is a ball-and-stick model. Note that in this representation appear many isolated red atoms
(oxygen) around the molecule. These are water molecules that are a part of the crystal structure of the protein. To see only
the protein structure, we use the command restrict not solvent:
In the next module we'll study the Secondary Structure of proteins.
Index