Structure of the S100A6 Complex with a Fragment from the C-Terminal Domain of Siah-1 Interacting Protein: A Novel Mode for S100 Protein Target Recognition

Lee, Young Tae; Dimitrova, Yoana N.; Schneider, Gabriela; Ridenour, Whitney B.; Bhattacharya, Shibani; Soss, Sarah E.; Caprioli, Richard M.; Filipek, Anna; Chazin, Walter J.

doi:10.1021/bi801233z

Cited by 63 publications

(91 citation statements)

References 45 publications

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“…We are currently attempting to crystallize the complex of TG2 and S100A4 which could reveal the detailed interaction sites of the proteins. So far all the known atomic-resolution complexes of S100 proteins display a linear motif of the partner that is localized in intrinsically disordered (ID) segments of the protein [16,[35][36][37]. This could be the case with TG2 where several ID segments were identified, although only in surface loops [2].…”

Section: Discussionmentioning

confidence: 99%

Metastasis-associated S100A4 is a specific amine donor and an activity-independent binding partner of transglutaminase-2

Biri

Kiss

Király

et al. 2015

Biochemical Journal

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Transglutaminase-2 (TG2) is best known as a Ca 2+ -dependent cross-linking enzyme; however, some of its extracellular matrix-related functions are independent from its catalytic activity and include matrix remodeling, adhesion and migration. S100A4 belongs to the Ca 2+ -binding EF-hand S100 protein family and acts both intra-and extracellularly through binding to various partners. It regulates cell migration and its overexpression is strongly associated with metastasis and poor survival in various cancers. TG2 has recently been suggested to mediate S100A4-dependent tumor cell migration. Here we provide evidence that S100A4 is an interacting partner and also specific amine donor of TG2. TG2 incorporates a glutamine donor peptide to Lys100 in the C-terminal random coil region of S100A4. Importantly, the enzyme activity is not necessary for the interaction: S100A4 also binds to TG2 in the presence of a specific inhibitor that keeps the enzyme in an open conformation, or to an enzymatically inactive mutant. We also found that S100A4 considerably enhances TG2-mediated adhesion of A431 epithelial carcinoma cells to the extracellular matrix. This role is independent of enzyme activity and requires the open conformation of TG2. We propose that S100A4 stabilizes the open conformation of TG2, which binds to its cell surface receptor in this state and increases cell adhesion.Summary: S100A4 and transglutaminase-2 have a role in metastasis. S100A4 is an interaction partner and specific amine substrate of transglutaminase-2, promoting its open conformation and leading to enhanced cell adhesion. Studying their interaction could contribute to the better understanding of metastasis.Running title: S100A4: substrate and binding partner of transglutaminase-2

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Section: Discussionmentioning

confidence: 99%

Metastasis-associated S100A4 is a specific amine donor and an activity-independent binding partner of transglutaminase-2

Biri

Kiss

Király

et al. 2015

Biochemical Journal

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“…Comparison of four peptide-bound S100 proteins. The structure of (A) S100A4-NMIIA (3ZWH), (B) S100A6-SIP (2JTT) (25), (C) S100A10-ANXA2 (1BT6) (21), and (D) S100B-p53 (1DT7) (22) Phosphorylation of NMIIA at Ser1916 by protein kinase C (43) appears to have little interference with binding the S100A4 dimer, as previously demonstrated experimentally (44), because the Ser1916 side chain points away from the binding interface (Fig. 3A).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, the known complex structures of the S100 family do not reveal a uniform binding mode as the orientations of the target peptides in each complex are considerably different. Nevertheless, all the structural models reveal that one S100 dimer binds symmetrically to two, predominantly α-helical peptide ligands (20)(21)(22)(23)(24)(25)(26).…”

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confidence: 99%

Crystal structure of the S100A4–nonmuscle myosin IIA tail fragment complex reveals an asymmetric target binding mechanism

Kiss

Duelli

Radnai

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

119

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S100A4 is a member of the S100 family of calcium-binding proteins that is directly involved in tumor metastasis. It binds to the nonmuscle myosin IIA (NMIIA) tail near the assembly competence domain (ACD) promoting filament disassembly, which could be associated with increasing metastatic potential of tumor cells. Here, we investigate the mechanism of S100A4-NMIIA interaction based on binding studies and the crystal structure of S100A4 in complex with a 45-residue-long myosin heavy chain fragment. Interestingly, we also find that S100A4 binds as strongly to a homologous heavy chain fragment of nonmuscle myosin IIC as to NMIIA. The structure of the S100A4-NMIIA complex reveals a unique mode of interaction in the S100 family: A single, predominantly α-helical myosin chain is wrapped around the Ca 2þ -bound S100A4 dimer occupying both hydrophobic binding pockets. Thermal denaturation experiments of coiled-coil forming NMIIA fragments indicate that the coiled-coil partially unwinds upon S100A4 binding. Based on these results, we propose a model for NMIIA filament disassembly: Part of the random coil tailpiece and the C-terminal residues of the coiled-coil are wrapped around an S100A4 dimer disrupting the ACD and resulting in filament dissociation. The description of the complex will facilitate the design of specific drugs that interfere with the S100A4-NMIIA interaction.

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“…Such a short helix is also observed in other Ca 2+ -loaded S100 proteins, for example S100A6 [protein data bank (PDB) entry 1K96], S100A8 (PDB entry 1MR8) or S100A9 (PDB entry 1IRJ) [45][46][47]. The C-terminal, classical EF-hand consists of helix III (52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62), the Ca 2+ -binding loop (63)(64)(65)(66)(67)(68)(69)(70)(71) and helix IV (72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89).…”

Section: +mentioning

confidence: 83%

“…Similarly to S100B, S100A1 binds peptides in the same region [65,66]. A different interaction mode was described for the complex of S100A6 with a peptide representing the binding site of Siah-1-interacting protein [67], where the peptide binds to the hydrophobic region between helix III and helix IV as well as to a region on top of the dimer interface. S100A2, S100A6 and S100B bind to p53 [37,[68][69][70]] in a Ca 2+ -dependent manner.…”

Section: Target Binding To S100a2mentioning

confidence: 99%

The structure of Ca²⁺‐loaded S100A2 at 1.3‐Å resolution

Koch

Fritz

2012

The FEBS Journal

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S100A2 is an EF-hand calcium ion (Ca 2+ )-binding protein that activates the tumour suppressor p53. In order to understand the molecular mechanisms underlying the Ca 2+ -induced activation of S100A2, the structure of Ca 2+ -bound S100A2 was determined at 1.3 Å resolution by X-ray crystallography. The structure was compared with Ca 2+ -free S100A2 and with other S100 proteins. Binding of Ca 2+ to S100A2 induces small structural changes in the N-terminal EF-hand, but a large conformational change in the C-terminal EF-hand, reorienting helix III by approximately 90°. This movement is accompanied by the exposure of a hydrophobic cavity between helix III and helix IV that represents the target protein interaction site. This molecular reorganization is associated with the breaking and new formation of intramolecular hydrophobic contacts. The target binding site exhibits unique features; in particular, the hydrophobic cavity is larger than in other Ca 2+ -loaded S100 proteins. The structural data underline that the shape and size of the hydrophobic cavity are major determinants for target specificity of S100 proteins and suggest that the binding mode for S100A2 is different from that of other p53-interacting S100 proteins.

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Structure of the S100A6 Complex with a Fragment from the C-Terminal Domain of Siah-1 Interacting Protein: A Novel Mode for S100 Protein Target Recognition

Cited by 63 publications

References 45 publications

Metastasis-associated S100A4 is a specific amine donor and an activity-independent binding partner of transglutaminase-2

Metastasis-associated S100A4 is a specific amine donor and an activity-independent binding partner of transglutaminase-2

Crystal structure of the S100A4–nonmuscle myosin IIA tail fragment complex reveals an asymmetric target binding mechanism

The structure of Ca²⁺‐loaded S100A2 at 1.3‐Å resolution

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Structure of the S100A6 Complex with a Fragment from the C-Terminal Domain of Siah-1 Interacting Protein: A Novel Mode for S100 Protein Target Recognition

Cited by 63 publications

References 45 publications

Metastasis-associated S100A4 is a specific amine donor and an activity-independent binding partner of transglutaminase-2

Metastasis-associated S100A4 is a specific amine donor and an activity-independent binding partner of transglutaminase-2

Crystal structure of the S100A4–nonmuscle myosin IIA tail fragment complex reveals an asymmetric target binding mechanism

The structure of Ca2+‐loaded S100A2 at 1.3‐Å resolution

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The structure of Ca²⁺‐loaded S100A2 at 1.3‐Å resolution