D. Tertiary Structure of Proteins

 

Introduction

The previous tutorials on secondary and supersecondary protein structure and the next two lectures on tertiary structure all go toward our goal of describing the overall structure of some very complex macromolecules. Why go into all this detail? A couple of reasons:

 

 

 

 

 

 

 

Tertiary structures and domains

The terms domain, fold, motif, and module are ill defined and may often be used loosely and interchangeably. For example, Jean-Renaud Garl (1992) offers the following seven definitions for a domain as a:

  1. stable unit that can be isolated by limited proteolysis or protein engineering
  2. structural unit visible at the atomic level by X-ray crystallography
  3. genetic unit which is deduced from comparison of primary sequences of DNA, RNA, or proteins, and which follows the inference that homologies in 'amino acid' sequences are associated with strong resemblances in tertiary structure.
  4. functional unit which is responsible for the whole or a part of a particular activity.
  5. evolutionary unit relating coding DNA sequences (exons) into particular protein structural units.
  6. thermodynamic unit which can fold and unfold in an all-or-none process and having two states: native and denatured.
  7. discrete unit which is the result of independent folding of a part of the polypeptide chain.

 

For our purposes we will define the domain as a structural unit . That is, it is a compact three dimensional structure resulting from the folding of a particular section of the polypeptide chain.

Hence, the domain is usually seen to be comprised of elements of secondary and supersecondary structure (or motifs) which may or may not be contiguous in the primary structure. Indeed the type of secondary structure present in the domain is used as a basis for classification of structural domains.

A domain is also seen to have more interactions within itself than with other part of the polypeptide chain. Figure 7.0 shows the organisation of polypeptide chains into structural domains.

A structural motif we have defined previously as an association of supersecondary structure.

The term module is also often used to describe the mosaic nature of proteins and we can define this as a contiguous section of a polypeptide which performs a particular function.

The term fold will, for our purposes, be considered equivalent to domain.

Consequently, tertiary structure can be used to describe the association of structural motifs within the domain and also the way the structural domains fit together. Things to note about structural domains:

 

 

 

 

 

 

Protein Tertiary Structure Classification

Domains, and their associated motif composition, can be used as a basis for classifying protein tertiary structure. However, there are various ways of defining, and using, a structural classification and some of these include:

SCOP (Structural Classification Of Proteins)

CATH (Class, Architecture, Topology, and Homologous Superfamily)

3Dee (Three Dimensional Protein Domain Definitions)

FSSP (Fold classification based on structure-structure alignment of Proteins)

There are also other 'nonstructural' ways of classifying proteins and include methods based on sequence identity (eg. Protfam) and sequence comparisons (eg. Prosite, Pfam, Blocks, ProDom, PIR, and Prints).

For this part of the course, however, we will concentrate on learning a little bit more about the SCOP classification. This classification stems from the work of Levitt and Chothia (1976) who grouped proteins according to the secondary structure composition of domains. According to this method proteins can be classified into five main groups:

  1. All alpha structure
  2. All beta structure
  3. Mixed alpha/beta structure
  4. Mixed alpha+beta structure
  5. Other Tertiary Structure


Introduction | Protein Hierarchy | Secondary Structure | Helices | Sheets | Loops | SuperSecondary Structure | Tertiary Structure | All alpha structure | All beta structure | Mixed alpha/beta structure | Mixed alpha+beta structure | Other Tertiary Structure
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