Module 6: Structure-Function Relationships


Protein Domains and Motifs

Protein structures module 6 contents Protein modeling back to the index of modules

"Super secondary" structure is based on the utility of different regions of a protein in the overall protein function(s). The types of such structures are:

  • Membrane-spanning (transmembrane) domain: Regions of a polypeptide that stretch through part or whole of the lipid bilayer membrane. This sequence is mostly hydrophobic.

  • Signal peptide domain: A 20-25 amino acid-long N-terminal end region of a polypeptide involved in membrane localization or secretion outside the cell. This sequence is also mostly hydrophobic.

  • Coiled Coil Motif: A motif containing parallel two-stranded coiled-coils. The sequences in the coils are usually in the alpha helix format.

  • Helix-turn-helix motif: Usually involved in binding to nucleic acids, particularly DNA.

Some web servers involved in domain or motif prediction:

  • Predict Protein Server from EMBL, Heidelberg, Germany. PredictProtein is a service for sequence analysis, and structure prediction.

  • SOSUI from Tokyo University of Agriculture & Technology, Japan. Classification and secondary structure Prediction of Membrane Proteins.

  • TMpred (transmembrane prediction) at ISREC (Swiss Institute for Experimental Cancer Research). The TMpred program makes a prediction of membrane-spanning regions and their orientation. The algorithm is based on the statistical analysis of TMbase, a database of naturally occurring transmembrane proteins. The prediction is made using a combination of several weight-matrices for scoring.

  • COILS (coiled coil prediction) at ISREC (Swiss Institute for Experimental Cancer Research). COILS is a program that compares a sequence to a database of known parallel two-stranded coiled-coils and derives a similarity score. By comparing this score to the distribution of scores in globular and coiled-coil proteins, the program then calculates the probability that the sequence will adopt a coiled-coil conformation.

  • SignalP (signal peptides) at the Technical University of Denmark. The SignalP World Wide Web server predicts the presence and location of signal peptide cleavage sites in amino acid sequences from different organisms: Gram-positive prokaryotes, Gram-negative prokaryotes, and eukaryotes.

Searching for patterns in proteins

  • One can search for patterns (the above-mentioned and other motifs & domains) in protein secondary structure. The best starting point for a pattern search is through databases such as,

    • Prosite: The Dictionary of Protein Sites & Patterns maintained by Amos Bairoch at University of Geneva, Switzerland.
    • BLOCKS: Developed & Maintained at the Fred Hutchinson Cancer Research Center in Seattle, Washington, USA.
    • ProDom: This database consists of an automatic compilation of homologous domains developed and maintained by Daniel Kahn at the INRA in Toulouse (France).

      Searching for patterns does not allow for gaps in the sequences to be compared and the matches have to be exact.

  • Other database search engines such as Pfam and PRINTS are useful in classifying proteins or regions within proteins into related families or as carrying common domains.

  • Profiles: This server compares a protein sequence to a generalized profile and it provides a very sensitive method for the discovery of distant sequence relationships. Such a profile is constructed from a family of related sequences that have undergone multiple alignments. A profile search, unlike a pattern search, allows gaps to be inserted into the query sequence for profile identification. (Example Figure of a Related G-Protein Domain)

Protein structures module 6 contents Protein modeling back to the index of modules

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