Structural Basis and IP6 Requirement for Pds5-Dependent Cohesin Dynamics

Zhuqing Ouyang; Ge Zheng; Diana R Tomchick; Xuelian Luo; Hongtao Yu

doi:10.1016/j.molcel.2016.02.033

Structural Basis and IP6 Requirement for Pds5-Dependent Cohesin Dynamics

Mol Cell. 2016 Apr 21;62(2):248-259. doi: 10.1016/j.molcel.2016.02.033. Epub 2016 Mar 10.

Authors

Zhuqing Ouyang¹, Ge Zheng¹, Diana R Tomchick², Xuelian Luo³, Hongtao Yu⁴

Affiliations

¹ Department of Pharmacology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.
² Department of Biophysics, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.
³ Department of Biophysics, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA; Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.
⁴ Department of Pharmacology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA. Electronic address: hongtao.yu@utsouthwestern.edu.

Abstract

The ring-shaped cohesin complex regulates transcription, DNA repair, and chromosome segregation by dynamically entrapping chromosomes to promote chromosome compaction and sister-chromatid cohesion. The cohesin ring needs to open and close to allow its loading to and release from chromosomes. Cohesin dynamics are controlled by the releasing factors Pds5 and Wapl and the cohesin stabilizer Sororin. Here, we report the crystal structure of human Pds5B bound to a conserved peptide motif found in both Wapl and Sororin. Our structure establishes the basis for how Wapl and Sororin antagonistically influence cohesin dynamics. The structure further reveals that Pds5 can bind inositol hexakisphosphate (IP6). The IP6-binding segment of Pds5B is shaped like the jaw of a plier lever and inhibits the binding of Scc1 to Smc3. We propose that Pds5 stabilizes a transient, open state of cohesin to promote its release from chromosomes.

MeSH terms

Adaptor Proteins, Signal Transducing / metabolism
Binding Sites
Carrier Proteins / metabolism
Cell Cycle Proteins / chemistry
Cell Cycle Proteins / metabolism*
Chondroitin Sulfate Proteoglycans / metabolism
Chromosomal Proteins, Non-Histone / chemistry
Chromosomal Proteins, Non-Histone / metabolism*
Chromosomes, Human / chemistry
Chromosomes, Human / genetics
Chromosomes, Human / metabolism*
Cohesins
Conserved Sequence
DNA-Binding Proteins / chemistry
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
HeLa Cells
Humans
Kinetics
Models, Molecular
Nuclear Proteins / metabolism
Phosphoproteins / metabolism
Phytic Acid / metabolism*
Protein Conformation
Protein Interaction Domains and Motifs
Proto-Oncogene Proteins / metabolism
RNA Interference
Structure-Activity Relationship
Transcription Factors / chemistry
Transcription Factors / genetics
Transcription Factors / metabolism*
Transfection

Substances

Adaptor Proteins, Signal Transducing
CDCA5 protein, human
Carrier Proteins
Cell Cycle Proteins
Chondroitin Sulfate Proteoglycans
Chromosomal Proteins, Non-Histone
DNA-Binding Proteins
Nuclear Proteins
PDS5B protein, human
Phosphoproteins
Proto-Oncogene Proteins
RAD21 protein, human
SMC3 protein, human
Transcription Factors
WAPL protein, human
Phytic Acid

Abstract

MeSH terms

Substances

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