BAG4/SODD protein contains a short BAG domain.
BAG (Bcl-2-associated athanogene) proteins are molecular chaperone regulators that affect diverse cellular pathways. All members share a conserved motif, called the BAG domain (BD), which binds to Hsp70/Hsc70 family proteins and modulates their activity. We have determined the solution structure of BD from BAG4/SODD (silencer of death domains) by multidimensional nuclear magnetic resonance methods and compared it to the corresponding domain in BAG1 (Briknarová, K., Takayama, S., Brive, L., Havert, M. L., Knee, D. A., Velasco, J., Homma, S., Cabezas, E., Stuart, J., Hoyt, D. W., Satterthwait, A. C., Llinás, M., Reed, J. C., and Ely, K. R. (2001) Nat. Struct. Biol. 8, 349-352). The difference between BDs from these two BAG proteins is striking, and the structural comparison defines two subfamilies of mammalian BD-containing proteins. One subfamily includes the closely related BAG3, BAG4, and BAG5 proteins, and the other is represented by BAG1, which contains a structurally and evolutionarily distinct BD. BDs from both BAG1 and BAG4 are three-helix bundles; however, in BAG4, each helix in this bundle is three to four turns shorter than its counterpart in BAG1, which reduces the length of the domain by one-third. BAG4 BD thus represents a prototype of the minimal functional fragment that is capable of binding to Hsc70 and modulating its chaperone activity.
Briknarová
Klara
K
Burnham Institute, La Jolla, CA 92037, USA.
Takayama
Shinichi
S
Homma
Sachiko
S
Baker
Kelly
K
Cabezas
Edelmira
E
Hoyt
David W
DW
Li
Zhen
Z
Satterthwait
Arnold C
AC
Ely
Kathryn R
KR
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000737:chemistry* / Q000502:physiology; D017124:Conserved Sequence; D004268:DNA-Binding Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; C116906:BAG4 protein, human; C091732:BCL2-associated athanogene 1 protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D008565:Membrane Proteins; D014157:Transcription Factors