Biomedical Engineering Reference
In-Depth Information
CHAPTER 5
NMR Studies of Disordered but
Functional Proteins
H. JANE DYSON
Department of Molecular Biology, The Scripps Research Institute,
10550 North Torrey Pines Road, La Jolla, CA 92037, USA
E-mail: dyson@scripps.edu
5.1 Introduction
The fundamental dogma of molecular biology states that the genetic
information encoded in deoxyribonucleotide sequences in DNA is transcribed
into the ribonucleotide sequence of messenger RNA and subsequently
translated by ribosomes into a sequence of amino acids in a protein. The
subsequent step in the process, where the linear amino acid sequence is folded
to form a three-dimensional (3D) structure is not yet completely understood.
Further, it now appears from bioinformatic and experimental studies that a
stable 3D structure may not be absolutely necessary for function, and indeed,
correct function in some cases may require that the protein be partly or fully
disordered.
The availability of complete genome sequences and consequent access to the
repertoire of possible protein sequences that could be derived from them led to
the rather unexpected observation that many of the polypeptide sequences coded
in the genomes would be clearly unable to fold into normal globular protein
structures.
1
The high frequency of small hydrophilic amino acids rendered these
sequences unlikely as candidates for membrane proteins or scaffolding proteins.
Interestingly, many of the proteins identified in these surveys, as well as in NMR
experimental studies that were ongoing at the same time, proved to be involved
