Kosloff
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Welcome to Mickey Kosloff's lab at the
Department of Human Biology,
Faculty of Natural Sciences,
The University of Haifa.
Our goals:
We focus on understanding how the �wiring together� of protein interaction
networks drives cellular communication in health and disease.
This is a fundamental challenge in studying and manipulating cellular
signal transduction
and in
rational drug design � we would like to decipher how
protein structure
encodes interaction specificity, thereby determining how signaling proteins
precisely recognize their interaction partners.
To achieve these goals, our lab combines computational and experimental
approaches in a multi-disciplinary strategy.
Click to contact us (and do mention you were clever enough to find this easter egg) Our main research activities:
1) Understanding the molecular basis for protein-protein interaction specificity
among large protein families. Current Research projects:
1) Develop computational and experimental approaches to decipher the
determinants of protein-protein interaction specificity at the family level.
More in-depth Background The challenge of deciphering interaction specificity among signaling protein families:
For signaling cascades to function correctly, their components must be �wired� together accurately.
This requirement presents a challenge for living cells, as similar components are used again and again
in both parallel and intersecting cascades within the same cell.
Signaling therefore requires that particular protein-protein interactions be tailored to each
signaling cascade with either broad or narrow specificity.
Understanding the basis for such selectivity is a major goal in biology, as well as in drug design.
Yet, beyond single representative examples, little is known of how specificity is determined in the
interactions between members of large protein families, including those involved in signal transduction.
Currently, computational methods are not up to the task of predicting either protein-protein or
protein-membrane binding affinities, although such methods can provide residue-level structural
insights and are easily scalable.
On the other hand, while quantitative experimental comparisons offer superior accuracy,
expanding such a comparative approach to the entire family level can be a daunting task,
and will usually fail to yield mechanistic insights at the resolution of individual residues.
Our solution to this conundrum is to combine the strengths of computations and experiments
into a multidisciplinary approach. RGS-G-proteins interactions - a model system to study interaction specificity:
The challenge of deciphering protein-protein interaction specificity is particularly relevant to the
interactions of heterotrimeric (alpha-beta-gamma) G-proteins with Regulators of G-protein Signaling (RGSs).
G-proteins are ubiquitous molecular switches that are essential for normal communication within and
between cells (see the
1994 Nobel prize in Physiology or medicine and the
2012 Nobel prize
in Chemistry).
RGS proteins are the negative regulators of G-alpha subunits,
functioning as GTPase Activating Proteins (GAPs).
Namely, the RGS domain of ~120 amino acids, present in all RGS proteins,
can bind specifically to certain GTP-associated G-alpha subunits and accelerate their intrinsic
GTPase activity allosterically.
Thereby, RGS proteins turn G-proteins �off� and determine the lifetime of the
activated G-protein switch.
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Typos for Mickey Kosloff (for Google):
Miki, Mikey, Micky, Micki, Nicki, Koslof,
Kozlov, Koslov, Kozloff, Kozalov.
Hebrew:
מיקי קוזלוב