TY - JOUR
T1 - There is Diversity in Disorder-"In all Chaos there is a Cosmos, in all Disorder a Secret Order"
AU - Nielsen, Jakob T
AU - Mulder, Frans A A
PY - 2016/2/11
Y1 - 2016/2/11
N2 - The protein universe consists of a continuum of structures ranging from full order to complete disorder. As the structured part of the proteome has been intensively studied, stably folded proteins are increasingly well documented and understood. However, proteins that are fully, or in large part, disordered are much less well characterized. Here we collected NMR chemical shifts in a small database for 117 protein sequences that are known to contain disorder. We demonstrate that NMR chemical shift data can be brought to bear as an exquisite judge of protein disorder at the residue level, and help in validation. With the help of secondary chemical shift analysis we demonstrate that the proteins in the database span the full spectrum of disorder, but still, largely segregate into two classes; disordered with small segments of order scattered along the sequence, and structured with small segments of disorder inserted between the different structured regions. A detailed analysis reveals that the distribution of order/disorder along the sequence shows a complex and asymmetric distribution, that is highly protein-dependent. Access to ratified training data further suggests an avenue to improving prediction of disorder from sequence.
AB - The protein universe consists of a continuum of structures ranging from full order to complete disorder. As the structured part of the proteome has been intensively studied, stably folded proteins are increasingly well documented and understood. However, proteins that are fully, or in large part, disordered are much less well characterized. Here we collected NMR chemical shifts in a small database for 117 protein sequences that are known to contain disorder. We demonstrate that NMR chemical shift data can be brought to bear as an exquisite judge of protein disorder at the residue level, and help in validation. With the help of secondary chemical shift analysis we demonstrate that the proteins in the database span the full spectrum of disorder, but still, largely segregate into two classes; disordered with small segments of order scattered along the sequence, and structured with small segments of disorder inserted between the different structured regions. A detailed analysis reveals that the distribution of order/disorder along the sequence shows a complex and asymmetric distribution, that is highly protein-dependent. Access to ratified training data further suggests an avenue to improving prediction of disorder from sequence.
KW - Chemical shift
KW - Data interpretation
KW - Intrinsically disordered proteins
KW - NMR spectroscopy
KW - Protein conformation
KW - Statistical
UR - http://www.scopus.com/inward/record.url?scp=85006836309&partnerID=8YFLogxK
U2 - 10.3389/fmolb.2016.00004
DO - 10.3389/fmolb.2016.00004
M3 - Journal article
C2 - 26904549
SN - 2296-889X
VL - 3
JO - Frontiers in Molecular Biosciences
JF - Frontiers in Molecular Biosciences
IS - FEB
M1 - 4
ER -