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



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