PMID- 14747656
OWN - NLM
STAT- MEDLINE
DCOM- 20040409
LR  - 20240322
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 101
IP  - 6
DP  - 2004 Feb 10
TI  - Stabilities of folding of clustered, two-repeat fragments of spectrin reveal a 
      potential hinge in the human erythroid spectrin tetramer.
PG  - 1502-7
AB  - The large size of spectrin, the flexible protein promoting reversible deformation 
      of red cells, has been an obstacle to elucidating the molecular mechanism of its 
      function. By studying cloned fragments of the repeating unit domain, we have 
      found a correspondence between positions of selected spectrin repeats in a 
      tetramer with their stabilities of folding. Six fragments consisting of two 
      spectrin repeats were selected for study primarily on the basis of the predicted 
      secondary structures of their linker regions. Fragments with a putatively helical 
      linker were more stable to urea- and heat-induced unfolding than those with a 
      putatively nonhelical linker. Two of the less stably folded fragments, human 
      erythroid alpha-spectrin repeats 13 and 14 (HEalpha13,14) and human erythroid 
      beta-spectrin repeats 8 and 9 (HEbeta8,9), are located opposite each other on 
      antiparallel spectrin dimers. At least partial unfolding of these repeats under 
      physiological conditions indicates that they may serve as a hinge. Also less 
      stably folded, the fragment of human erythroid alpha-spectrin repeats 4 and 5 
      (HEalpha4,5) lies opposite the site of interaction between the partial repeats at 
      the C- and N-terminal ends of beta- and alpha-spectrin, respectively, on the 
      opposing dimer. More stably folded fragments, human erythroid alpha-spectrin 
      repeats 1 and 2 (HEalpha1,2) and human erythroid alpha-spectrin repeats 2 and 3 
      (HEalpha2,3), lie nearly opposite each other on antiparallel spectrin dimers of a 
      tetramer. These clusterings along the spectrin tetramer of repeats with similar 
      stabilities of folding may have relevance for spectrin function, particularly for 
      its well known flexibility.
FAU - MacDonald, Ruby I
AU  - MacDonald RI
AD  - Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern 
      University, Evanston, IL 60208, USA. rubymacd@northwestern.edu
FAU - Cummings, Julie A
AU  - Cummings JA
LA  - eng
GR  - R01 GM057692/GM/NIGMS NIH HHS/United States
GR  - GM 57692/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040127
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 12634-43-4 (Spectrin)
SB  - IM
MH  - Humans
MH  - Protein Folding
MH  - Protein Structure, Secondary
MH  - Spectrin/chemistry/genetics/*metabolism
PMC - PMC341761
EDAT- 2004/01/30 05:00
MHDA- 2004/04/10 05:00
PMCR- 2004/08/10
CRDT- 2004/01/30 05:00
PHST- 2004/01/30 05:00 [pubmed]
PHST- 2004/04/10 05:00 [medline]
PHST- 2004/01/30 05:00 [entrez]
PHST- 2004/08/10 00:00 [pmc-release]
AID - 0308059100 [pii]
AID - 1011502 [pii]
AID - 10.1073/pnas.0308059100 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1502-7. doi: 
      10.1073/pnas.0308059100. Epub 2004 Jan 27.