Computation and Functional Studies Provide a Model for the Structure of the Zinc Transporter hZIP4

Antala, Sagar; Овчинников, С. Г.; Kamisetty, Hetunandan; Baker, David; Dempski, Robert E.

doi:10.1074/jbc.m114.617613

Cited by 67 publications

(84 citation statements)

References 49 publications

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“…An alternative approach is to first build a model using homology modeling or Rosetta, either of which can often generate decent model structures, then use the evolutionary coupling constraints to refine or expand the structural model [120]. This approach has been applied to the human zinc-regulated transporter protein hZIP4, where Rosetta and evolutionary constraints helped build a dimeric model of the transporter [121]. Recently, a structure of a ZIP from the bacterium Bordetella bronchiseptica was solved that has a 4 Å rmsd (over ~200 C α ) with the Rosetta model with evolutionary constraints [122].…”

Section: Integrative Modeling Of Membrane Protein Structurementioning

confidence: 99%

Applications of sequence coevolution in membrane protein biochemistry

Nicoludis¹,

Gaudet²

2018

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Recently, protein sequence coevolution analysis has matured into a predictive powerhouse for protein structure and function. Direct methods, which use global statistical models of sequence coevolution, have enabled the prediction of membrane and disordered protein structures, protein complex architectures, and the functional effects of mutations in proteins. The field of membrane protein biochemistry and structural biology has embraced these computational techniques, which provide functional and structural information in an otherwise experimentally-challenging field. Here we review recent applications of protein sequence coevolution analysis to membrane protein structure and function and highlight the promising directions and future obstacles in these fields. We provide insights and guidelines for membrane protein biochemists who wish to apply sequence coevolution analysis to a given experimental system.

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Section: Integrative Modeling Of Membrane Protein Structurementioning

confidence: 99%

Applications of sequence coevolution in membrane protein biochemistry

Nicoludis¹,

Gaudet²

2018

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…Such contact predictions have been used for a wide range of protein modeling efforts (11 – 22). Accurate contact prediction requires large numbers of aligned sequences so that residue-residue covariance is clearly distinguished from lineage effects.…”

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confidence: 99%

Protein structure determination using metagenome sequence data

Овчинников

Park

Varghese

et al. 2017

Science

Self Cite

491

574

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Despite decades of work by structural biologists, there are still ~5200 protein families with unknown structure outside the range of comparative modeling. We show that Rosetta structure prediction guided by residue-residue contacts inferred from evolutionary information can accurately model proteins that belong to large families, and that metagenome sequence data more than triples the number of protein families with sufficient sequences for accurate modeling. We then integrate metagenome data, contact based structure matching and Rosetta structure calculations to generate models for 614 protein families with currently unknown structures; 206 are membrane proteins and 137 have folds not represented in the PDB. This approach provides the representative models for large protein families originally envisioned as the goal of the protein structure initiative at a fraction of the cost.

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“…While ZIP transporters are members of the cation diffusion facilitator class of proteins, ZnT proteins are not. Comparison of the crystal structure of YiiP, a bacterial ZnT protein with an ab initio model of the human (h) ZIP4 transporter suggests that both protein families have a similar transmembrane metal coordination site [15,16]. Both ZnT and ZIP proteins are expressed on the plasma membrane as well as on the membranes of intracellular organelles.…”

Section: Introductionmentioning

confidence: 99%

Zn2+ at a cellular crossroads

Liang

Dempski

Burdette

2016

Current Opinion in Chemical Biology

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Zinc is an essential micronutrient for cellular homeostasis. Initially proposed to only contribute to cellular viability through structural roles and non-redox catalysis, advances in quantifying changes in nM and pM quantities of Zn2+ have elucidated increasing functions as an important signaling molecule. This includes Zn2+-mediated regulation of transcription factors and subsequent protein expression, storage and release of intracellular compartments of zinc quanta into the extracellular space which modulates plasma membrane protein function, as well as intracellular signaling pathways which contribute to the immune response. This review highlights some recent advances in our understanding of zinc signaling.

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Computation and Functional Studies Provide a Model for the Structure of the Zinc Transporter hZIP4

Cited by 67 publications

References 49 publications

Applications of sequence coevolution in membrane protein biochemistry

Applications of sequence coevolution in membrane protein biochemistry

Protein structure determination using metagenome sequence data

Zn2+ at a cellular crossroads

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