Chemistry Reference
In-Depth Information
NMR as a Unique Tool in Assessment
and Complex Determination of Weak
Protein-Protein Interactions
Olga Vinogradova and Jun Qin
Abstract Protein-protein interactions are crucial for a wide variety of biological
processes. These interactions range from high affinity (
K
d
<
nM) to very low
affinity (
K
d
>
mM). While much is known about the nature of high affinity protein
complexes, our knowledge about structural characteristics of weak protein-protein
interactions (wPPIs) remains limited: in addition to the technical difficulties
associated with their investigation, historically wPPIs used to be considered physio-
logically irrelevant. However, emerging evidence suggests that wPPIs, either in the
form of intact protein complexes or as part of large molecular machineries, are
fundamentally important for promoting rapid on/off switches of signal transduc-
tion, reversible cell-cell contacts, transient assembly/disassembly of signaling
complexes, and enzyme-substrate recognition. Therefore an atomic-level elucida-
tion of wPPIs is vital to understanding a cornucopia of diverse cellular events.
Nuclear magnetic resonance (NMR) is famous for its unique abilities to study
wPPIs and, by utilization of the new technical developments combined with sparse
data based computational analysis, it now allows rapid identification and structural
characterization of wPPIs. Here we present our perspective on the NMR methods
employed.
Keywords Chemical shifts
NMR
NOE
PCS
PRE
RDC
