Crystal structure of calsequestrin from rabbit skeletal muscle sarcoplasmic reticulum.
Calsequestrin, the major Ca2+ storage protein of muscle, coordinately binds and releases 40-50 Ca2+ ions per molecule for each contraction-relaxation cycle by an uncertain mechanism. We have determined the structure of rabbit skeletal muscle calsequestrin. Three very negative thioredoxin-like domains surround a hydrophilic center. Each monomer makes two extensive dimerization contacts, both of which involve the approach of many negative groups. This structure suggests a mechanism by which calsequestrin may achieve high capacity Ca2+ binding. The suggested mechanism involves Ca2+-induced collapse of the three domains and polymerization of calsequestrin monomers arising from three factors: N-terminal arm exchange, helix-helix contacts and Ca2+ cross bridges. This proposed structure-based mechanism accounts for the observed coupling of high capacity Ca2+ binding with protein precipitation.
Wang
S
S
Department of Biochemistry and Biophysics, Washington State University, Pullman 99164-4660, USA.
Trumble
W R
WR
Liao
H
H
Wesson
C R
CR
Dunker
A K
AK
Kang
C H
CH
D000818:Animals; D001704:Biopolymers / Q000737:chemistry; D002135:Calcium-Binding Proteins / Q000737:chemistry; D002155:Calsequestrin / Q000737:chemistry*; D003460:Crystallization; D018360:Crystallography, X-Ray; D019281:Dimerization; D008954:Models, Biological; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000737:chemistry*
D001704:Biopolymers; D002135:Calcium-Binding Proteins; D002155:Calsequestrin