Philip Graceffa, Ph.D.
Senior Scientist
Smooth-muscle related diseases, e.g. cardiovascular disease, asthma and stroke
Email: graceffa at bbri.org

Research Summary
Blood vessel smooth muscle regulates blood flow by either contracting to constrict vessel diameter or relaxing to increase vessel diameter. The smooth muscle thin filament is primarily comprised of the protein actin along with the two actin binding proteins, tropomyosin and caldesmon, which are thought to regulate contraction and the economic maintenance of force. We have been studying the contractile function of caldesmon using a variety of crosslinking, fluorescent and magnetic probes. In collaboration with Dr. Roberto Dominguez, we also have been investigating the detailed atomic crystal structure of actin in complex with other smooth muscle contractile proteins to understand the unique contractile properties of smooth muscle.

Electrophoretic pattern before (A) and after (B) treatment of a mixture of caldesmon (CaD) and actin with a crosslinking reagent DTNB. The product (band X) is due to a bond between the C-terminal domains of both proteins.

Selected Publications
Graceffa, P., & Mazurkie, A., Effect of caldesmon on the position and myosin-induced movement of smooth muscle tropomyosin bound to actin, J. Biol. Chem. 280(6):4135-43 (2005)

Graceffa, P. & Dominguez, R., Crystal structure of monomeric actin in the ATP state. Structural basis of nucleotide-dependent actin dynamics, J. Biol. Chem. 278:34172-34180 (2003)

Dominguez, R. & Graceffa, P., Solution properties of TMR-actin: when biochemical and crystal data agree, Biophys. J. 85:2073-2074 (2003)

Otterbein, L., Graceffa, P., & Dominguez, R., The Crystal Structure of Uncomplexed G-actin in the ADP State, Science 293:708-711 (2001)

Mabuchi, K., Carlos, A., Li, Y.-H., Wang C.-L. A., & Graceffa, P., Caldesmon Exhibits a Clustered Distribution Along Individual Chicken Gizzard Native Thin Filaments, J. Muscle Res. Cell Motil. 22:77-90 (2001)

Graceffa, P. Phosphorylation of smooth muscle myosin heads regulates the head-induced movement of tropomyosin. J. Biol. Chem. 275:17145-17148 (2000)

PubMed:
Click here for a list of publications (searches the National Library of Medicine's PubMed database.)