Structures of calmodulin and a functional myosin light chain kinase in the activated complex: a neutron scattering study

Biochemistry
J K KruegerJ Trewhella

Abstract

Calmodulin (CaM) is the major intracellular receptor for Ca2+ and is responsible for the Ca2+-dependent regulation of a wide variety of cellular processes via interactions with a diverse array of target enzymes. Our current view of the structural basis for CaM enzyme activation is based on biophysical studies of CaM complexed with small peptides that model CaM-binding domains. A major concern with interpreting data from these structures in terms of target enzyme activation mechanisms is that the larger enzyme structure might be expected to impose constraints on CaM binding. Full understanding of the molecular mechanism for CaM-dependent enzyme activation requires additional structural information on the interaction of CaM with functional enzymes. We have utilized small-angle X-ray scattering and neutron scattering with contrast variation to obtain the first structural view of CaM complexed with a functional enzyme, an enzymatically active truncation mutant of skeletal muscle myosin light chain kinase (MLCK). Our data show that CaM undergoes an unhindered conformational collapse upon binding MLCK and activates the enzyme by inducing a significant movement of the kinase's CaM binding and autoinhibitory sequences away from the sur...Continue Reading

References

Apr 5, 1975·Journal of Molecular Biology·K Ibel
Aug 13, 1991·Biochimica Et Biophysica Acta·B E Kemp, R B Pearson
Nov 5, 1988·Journal of Molecular Biology·Y S BabuW J Cook
May 2, 1985·Nature·Y S BabuW J Cook
Sep 1, 1995·Nature Structural Biology·H KuboniwaA Bax
Sep 1, 1995·Nature Structural Biology·B E FinnS Forsén
Jul 14, 1995·The Journal of Biological Chemistry·J K KruegerJ T Stull
Nov 1, 1993·Molecular and Cellular Biochemistry·M C FauxB E Kemp

❮ Previous
Next ❯

Citations

Mar 2, 2011·Journal of Biomolecular NMR·Jessica L GiffordHans J Vogel
Nov 7, 1998·Biochimica Et Biophysica Acta·A ArbuzovaS McLaughlin
Nov 5, 1997·Current Opinion in Structural Biology·J Trewhella
Jul 8, 2000·Trends in Cell Biology·D Chin, A R Means
Jan 25, 2011·The Journal of Biological Chemistry·Kristine E Kamm, James T Stull
Mar 27, 2001·Annual Review of Pharmacology and Toxicology·S S Hook, A R Means
Oct 14, 2000·Annual Review of Physical Chemistry·M E WallJ Trewhella
Jan 15, 1999·Acta Physiologica Scandinavica·J T StullG Zhi
May 14, 2011·Archives of Biochemistry and Biophysics·Feng HongChristine R Cremo
Feb 3, 2011·Archives of Biochemistry and Biophysics·James T StullRene Vandenboom
May 13, 2015·Bioorganic & Medicinal Chemistry·Bertrand SimonMatthias Wilmanns
Apr 28, 2001·Biophysical Journal·D VigilA E García
Dec 24, 2002·Biophysical Journal·Maxim V PetoukhovDmitri I Svergun
Jun 22, 2016·Proceedings of the National Academy of Sciences of the United States of America·Audrey N ChangJames T Stull
Oct 16, 2016·Journal of Molecular and Cellular Cardiology·Audrey N ChangJames T Stull
Mar 30, 2001·The Journal of Biological Chemistry·R D BrokxG I Makhatadze
Apr 3, 2013·Current Protocols in Protein Science·John F AnknerDean A A Myles
Feb 20, 1999·The Journal of Biological Chemistry·P LinJ T Stull
Mar 30, 2001·The Journal of Biological Chemistry·I K FeilD I Svergun
Oct 9, 1998·The Journal of Biological Chemistry·S J Lee, J T Stull
May 16, 1998·The Journal of Biological Chemistry·G ZhiJ T Stull
Oct 27, 1997·The Journal of Biological Chemistry·A ArbuzovaS McLaughlin
Dec 22, 2000·The Journal of Biological Chemistry·J K KruegerJ Trewhella
Feb 8, 2000·The Journal of Biological Chemistry·A PersechiniP M Stemmer
Feb 1, 2017·Biochemistry and Biophysics Reports·Elddie Román-MoralesJuan López-Garriga
May 29, 1999·Biochemistry·S C GallagherJ Trewhella
Dec 26, 2001·Chemical Reviews·T R Soderling, J T Stull

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.