TY - JOUR
T1 - Structural insights into the stability and flexibility of unusual erythroid spectrin repeats
AU - Kusunoki, Hideki
AU - MacDonald, Ruby I.
AU - Mondragón, Alfonso
N1 - Funding Information:
We gratefully acknowledge the contributions of J. Bosman and K.A. Swanson to the initial stages of this project. We thank B. Forget for the cDNA of human β-erythroid spectrin, G. Minasov and P. Focia for their help and advice, G. Minasov, I. Radhakrishnan, and J. Widom for comments on the manuscript, and the Keck Biophysics Facility of Northwestern University for instrument support. Support from the R.H. Lurie Comprehensive Cancer Center of Northwestern University to the Structural Biology Facility is acknowledged. Research was supported by an NIH grant to R.I.M. and A.M. Portions of this work were performed at the DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) Synchrotron Research Center at the Advanced Photon Source (APS). DND-CAT is supported by Dupont, Dow, and the NSF. Use of the APS is supported by the Department of Energy (DOE).
PY - 2004/4
Y1 - 2004/4
N2 - Erythroid spectrin, a major component of the cytoskeletal network of the red cell which contributes to both the stability and the elasticity of the red cell membrane, is composed of two subunits, α and β, each formed by 16-20 tandem repeats. The properties of the repeats and their relative arrangement are thought to be key determinants of spectrin flexibility. Here we report a 2.4 Å resolution crystal structure of human erythroid β-spectrin repeats 8 and 9. This two-repeat fragment is unusual as it exhibits low stability of folding and one of its repeats lacks two tryptophans highly conserved among spectrin repeats. Two key factors responsible for the lower stability and, possibly, its flexibility, are revealed by the structure. A third novel feature of the structure is the relative orientation of the two repeats, which increases the range of possible conformations and provides new insights into atomic models of spectrin flexibility.
AB - Erythroid spectrin, a major component of the cytoskeletal network of the red cell which contributes to both the stability and the elasticity of the red cell membrane, is composed of two subunits, α and β, each formed by 16-20 tandem repeats. The properties of the repeats and their relative arrangement are thought to be key determinants of spectrin flexibility. Here we report a 2.4 Å resolution crystal structure of human erythroid β-spectrin repeats 8 and 9. This two-repeat fragment is unusual as it exhibits low stability of folding and one of its repeats lacks two tryptophans highly conserved among spectrin repeats. Two key factors responsible for the lower stability and, possibly, its flexibility, are revealed by the structure. A third novel feature of the structure is the relative orientation of the two repeats, which increases the range of possible conformations and provides new insights into atomic models of spectrin flexibility.
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U2 - 10.1016/j.str.2004.02.022
DO - 10.1016/j.str.2004.02.022
M3 - Article
C2 - 15062087
AN - SCOPUS:1842450320
SN - 0969-2126
VL - 12
SP - 645
EP - 656
JO - Structure with Folding & design
JF - Structure with Folding & design
IS - 4
ER -