title: Solution structure of human Mts1 (S100A4) as determined by NMR spectroscopy.
abstract: Mts1 is a member of the S100 family of Ca2+-binding proteins and is implicated in promoting tumor progression and metastasis. To better understand the structure-function relationships of this protein and to begin characterizing its Ca2+-dependent interaction with protein binding targets, the three-dimensional structure of mts1 was determined in the apo state by NMR spectroscopy. As with other S100 protein family members, mts1 is a symmetric homodimer held together by noncovalent interactions between two helices from each subunit (helices 1, 4, 1', and 4') to form an X-type four-helix bundle. Each subunit of mts1 has two EF-hand Ca2+-binding domains: a pseudo-EF-hand (or S100-hand) and a typical EF-hand that are brought into proximity by a small two-stranded antiparallel beta-sheet. The S100-hand is formed by helices 1 and 2, and is similar in conformation to other members of the S100 family. In the typical EF-hand, the position of helix 3 is similar to that of another member of the S100 protein family, calcyclin (S100A6), and less like that of other S100 family members for which three-dimensional structures are available in the calcium-free state (e.g., S100B and S100A1). The differences in the position of helix 3 in the apo state of these four S100 proteins are likely due to variations in the amino acid sequence in the C-terminus of helix 4 and in loop 2 (the hinge region) and could potentially be used to subclassify the S100 protein family.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, Maryland 21201, USA.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Vallely
authors.forename: Richard R
authors.initials: RR
authors.lastname: Rustandi
authors.forename: Karen C
authors.initials: KC
authors.lastname: Ellis
authors.forename: Olga
authors.initials: O
authors.lastname: Varlamova
authors.forename: Anne R
authors.initials: AR
authors.lastname: Bresnick
authors.forename: David J
authors.initials: DJ
authors.lastname: Weber
mesh_terms: D000595:Amino Acid Sequence; D001059:Apoproteins / Q000737:chemistry; D002135:Calcium-Binding Proteins / Q000737:chemistry; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D040681:Structural Homology, Protein
chemical_list: D001059:Apoproteins; D002135:Calcium-Binding Proteins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D012996:Solutions; C077591:S100A4 protein, human