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Examination of the structure and dynamics of the calcium‐binding protein S100A5
Author(s) -
Liriano Melissa Ana,
Varney Kristen M.,
Wright Nathan T.,
Wilder Paul T.,
Charpentier Thomas H.,
Weber David J.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.885.1
Subject(s) - ef hand , calcium binding protein , chemistry , conformational change , calmodulin , calcium , biophysics , molecular dynamics , protein structure , nuclear magnetic resonance spectroscopy , crystallography , s100 protein , heteronuclear single quantum coherence spectroscopy , biochemistry , stereochemistry , biology , computational chemistry , immunohistochemistry , organic chemistry , immunology
The S100 family is a class of small, homodimeric proteins that are often characterized by their Ca 2+ ‐dependent biological effects, which is typically the result of a calcium‐dependent conformational change. To characterize whether S100A5 undergoes a conformational change similar to that observed in other S100 proteins, we will first determine the high resolution structure of this protein by NMR in the absence and presence of calcium. The HSQC spectras we have obtained of S100A5 depicts vast chemical shift pertubations from no calcium to calcium‐loaded S100A5, which is highly suggestive of a conformational change. S100A5 shares approximately 50% sequence homology with all the other S100 proteins yet it binds to Ca 2+ with an affinity 10‐100 times greater then any other S100 member. We hypothesize that the high affinity of S100A5 is due to either a structural difference between S100A5 and other S100 proteins or that A5 lacks the dynamic properties observed in the C‐terminal region of other S100 proteins that could contribute to their lesser affinity for Ca 2+ . In order to elucidate which mechanism is the basis of A5's high affinity for Ca 2+ , we propose to also solve the Ca 2+ ‐bound S100A5 using X‐ray crystallography to determine if there is an additional Ca 2+ ion ligand present. Internal dynamics will also be measured using 15 N NMR relaxation methods to prove whether or not S100A5 lacks dynamic properties in the C‐terminal EF‐hand. Student support provided by an NIGMS Initiative for Maximizing Student Diversity Grant (R25‐GM 55036)