Mutations in muscle-type creatine kinase impact HIV prevention

2021 ◽  
Author(s):  
Julia M. Migliorati ◽  
Xiao-bo Zhong
Keyword(s):  
Creatine Kinase ◽  
Hiv Prevention ◽  
Muscle Type

Slow skeletal muscle myosin-binding protein-C (MyBPC1) mediates recruitment of muscle-type creatine kinase (CK) to myosin

2011 ◽  
Vol 436 (2) ◽  
pp. 437-445 ◽  
Author(s):  
Zhe Chen ◽  
Tong-Jin Zhao ◽  
Jie Li ◽  
Yan-Song Gao ◽  
Fan-Guo Meng ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Creatine Kinase ◽  
Muscle Contraction ◽  
Binding Protein ◽  
High Energy ◽  
Functional Coupling ◽  
Muscle Type ◽  
Myosin Binding Protein ◽  
Slow Skeletal Muscle ◽  
Myosin Binding

Muscle contraction requires high energy fluxes, which are supplied by MM-CK (muscle-type creatine kinase) which couples to the myofibril. However, little is known about the detailed molecular mechanisms of how MM-CK participates in and is regulated during muscle contraction. In the present study, MM-CK is found to physically interact with the slow skeletal muscle-type MyBPC1 (myosin-binding protein C1). The interaction between MyBPC1 and MM-CK depended on the creatine concentration in a dose-dependent manner, but not on ATP, ADP or phosphocreatine. The MyBPC1–CK interaction favoured acidic conditions, and the two molecules dissociated at above pH 7.5. Domain-mapping experiments indicated that MM-CK binds to the C-terminal domains of MyBPC1, which is also the binding site of myosin. The functional coupling of myosin, MyBPC1 and MM-CK is further corroborated using an ATPase activity assay in which ATP expenditure accelerates upon the association of the three proteins, and the apparent Km value of myosin is therefore reduced. The results of the present study suggest that MyBPC1 acts as an adaptor to connect the ATP consumer (myosin) and the regenerator (MM-CK) for efficient energy metabolism and homoeostasis.

Cellular distributions of creatine kinase in branchia of euryhaline tilapia (Oreochromis mossambicus)

2003 ◽  
Vol 284 (1) ◽  
pp. C233-C241 ◽  
Author(s):  
Li-Yih Lin ◽  
Chia-Chang Chiang ◽  
Hong-Yi Gong ◽  
Ching-Yi Cheng ◽  
Pung-Pung Hwang ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Cellular Localization ◽  
Potential Role ◽  
Oreochromis Mossambicus ◽  
Staining Intensity ◽  
Muscle Type ◽  
Environmental Fluctuation ◽  
High Association ◽  
Salinity Changes

Although euryhaline teleosts can adapt to environmental fluctuation of salinity, their energy source for responding to changes in salinity and osmolarity remains unclear. This study examines the cellular localization of creatine kinase (CK) expression in branchia of tilapia ( Oreochromis mossambicus). Western blot analysis of muscle-type CK (MM form) revealed a high association with salinity changes, but BB and MB forms of CK in the gills of fish adapted to seawater did not change. With the use of immunocytochemistry, three CK isoforms (MM, MB, and BB) were localized in mitochondria-rich (MR) cells and other epithelial cells of tilapia gills. In addition, staining intensity of MM-form CK in MR cells increased after seawater transfer, whereas BB and MB forms did not significantly change. To our knowledge, this work presents the first evidence of CK expression in MR cells of tilapia gills, highlighting the potential role of CK in providing energy for ion transport.

scholarly journals A monoclonal antibody to human brain-type creatine kinase. Increased avidity with mercaptans

1983 ◽  
Vol 215 (3) ◽  
pp. 505-512 ◽  
Author(s):  
A P Jackson ◽  
K Siddle ◽  
R J Thompson
Keyword(s):  
Molecular Weight ◽  
Monoclonal Antibody ◽  
Creatine Kinase ◽  
Human Brain ◽  
Binding Constant ◽  
Partial Reduction ◽  
Muscle Type ◽  
Antibody Molecule ◽  
Disulphide Bonds ◽  
Antibody Subclass

1. A monoclonal antibody (subclass immunoglobulin G1) has been raised against human brain-type creatine kinase (CK-BB). This antibody did not cross-react with either muscle-type creatine kinase (CK-MM) or heart-type creatine kinase (CK-MB). 2. The binding constant measured with native antibody was 6 X 10(8) M-1. In the presence of 2mM-dithiothreitol this constant was some 40-50-fold greater. 3. Partial reduction and alkylation showed that the increased binding was due to a direct effect on the antibody and was associated with concomitant cleavage of the heavy-heavy interchain disulphide bonds. The binding constant measured with Fab' fragments produced from reduced and alkylated antibody was similar to that shown by the native, unreduced antibody. 4. The molecular weight of the complex found in the absence of mercaptans was consistent with one antibody and one CK-BB molecule, whereas the molecular weight estimated with reduced and alkylated antibody was consistent with a complex of two antibodies and two CK-BB molecules. 5. It is proposed that mercaptans increase the flexibility of the hinge region of the antibody molecule, allowing the formation of a higher-order complex with increased avidity for the CK-BB dimer.

Mutation of conserved active-site threonine residues in creatine kinase affects autophosphorylation and enzyme kinetics

2002 ◽  
Vol 363 (3) ◽  
pp. 785-792 ◽  
Author(s):  
Martin STOLZ ◽  
Thorsten HORNEMANN ◽  
Uwe SCHLATTNER ◽  
Theo WALLIMANN
Keyword(s):  
Creatine Kinase ◽  
Isoelectric Focusing ◽  
Active Site ◽  
Catalytic Mechanism ◽  
Phosphorylation Sites ◽  
Enzyme Kinetic ◽  
Two Dimensional ◽  
Muscle Type ◽  
Cellular Energetics ◽  
Phosphoamino Acid Analysis

Muscle-type creatine kinase (MM-CK) is a member of an isoenzyme family with key functions in cellular energetics. It has become a matter of debate whether the enzyme is autophosphorylated, as reported earlier [Hemmer, Furter-Graves, Frank, Wallimann and Furter (1995) Biochim. Biophys. Acta 1251, 81–90], or exclusively nucleotidylated. In the present paper, we demonstrate unambiguously that CK is indeed autophosphorylated. However, this autophosphorylation is not solely responsible for the observed microheterogeneity of MM-CK on two-dimensional isoelectric focusing gels. Using phosphoamino-acid analysis of 32P-labelled CK isoforms, phosphothreonine (P-Thr) residues were identified as the only product of autophosphorylation for all CK isoenzymes. The phosphorylated residues in chicken MM-CK were allocated to a region in the vicinity of the active site, where five putative phosphorylation sites were identified. Site-directed threonine—valine-replacement mutants reveal that autophosphorylation is not specific for one particular residue but occurs at all examined threonine residues. The enzyme kinetic parameters indicate that the autophosphorylation of CK exerts a modulatory effect on substrate binding and the equilibrium constant, rather than on the catalytic mechanism itself.

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