Biochemical and bioinformatic analysis of the myosin-XIX motor domain.

Autor: Adikes RC; Program in Biochemistry, Mount Holyoke College, South Hadley, Massachusetts, USA., Unrath WC, Yengo CM, Quintero OA
Jazyk: angličtina
Zdroj: Cytoskeleton (Hoboken, N.J.) [Cytoskeleton (Hoboken)] 2013 May; Vol. 70 (5), pp. 281-95. Date of Electronic Publication: 2013 May 02.
DOI: 10.1002/cm.21110
Abstrakt: Mitochondrial dynamics are dependent on both the microtubule and actin cytoskeletal systems. Evidence for the involvement of myosin motors has been described in many systems, and until recently a candidate mitochondrial myosin transport motor had not been described in vertebrates. Myosin-XIX (MYO19) was predicted to represent a novel class of myosin and had previously been shown to bind to mitochondria and increase mitochondrial network dynamics when ectopically expressed. Our analyses comparing ∼40 MYO19 orthologs to ∼2000 other myosin motor domain sequences identified instances of homology well-conserved within class XIX myosins that were not found in other myosin classes, suggesting MYO19-specific mechanochemistry. Steady-state biochemical analyses of the MYO19 motor domain indicate that Homo sapiens MYO19 is a functional motor. Insect cell-expressed constructs bound calmodulin as a light chain at the predicted stoichiometry and displayed actin-activated ATPase activity. MYO19 constructs demonstrated high actin affinity in the presence of ATP in actin-co-sedimentation assays, and translocated actin filaments in gliding assays. Expression of GFP-MYO19 containing a mutation impairing ATPase activity did not enhance mitochondrial network dynamics, as occurs with wild-type MYO19, indicating that myosin motor activity is required for mitochondrial motility. The measured biochemical properties of MYO19 suggest it is a high-duty ratio motor that could serve to transport mitochondria or anchor mitochondria, depending upon the cellular microenvironment.
(Copyright © 2013 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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