Jeremy Liew

University of Massachusetts Boston

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Daniel P. Dowling

University of Massachusetts Boston

Denyce K. Wicht

Suffolk University

Ngan Thi Ngoc Phan

Son V. Nguyen

University of New Hampshire

Israa M. El Saudi

Saarland University

Alexey Veraksa

University of Massachusetts Boston

Marta Forés

Institut de Biologia Molecular de Barcelona

Sayantanee Paul

University of Massachusetts Boston

Gerardo Jiménez

Institut de Biologia Molecular de Barcelona

Andrew Gnann

University of Massachusetts Boston

Cooperative Institutions

University of Massachusetts Boston

Suffolk University

University of California, San Diego

University of Massachusetts Amherst

Massachusetts Institute of Technology

Institut de Biologia Molecular de Barcelona

Consejo Superior de Investigaciones Científicas

University of Arizona

Howard Hughes Medical Institute

Massachusetts General Hospital

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Molecular basis of DNA recognition by the HMG-box-C1 module of Capicua

bioRxiv (Cold Spring Harbor Laboratory) (2022)

Jonathan Webb Jeremy Liew Andrew Gnann MacKenzie Patterson Sayantanee Paul

Abstract The HMG-box protein Capicua (CIC) is an evolutionarily conserved transcriptional repressor with key functions in development and disease-associated processes. CIC binds DNA using an exclusive mechanism that requires both its HMG-box and a separate domain called C1, but how these domains cooperate to recognize specific DNA sequences is not known. Here we report the crystal structure of the human CIC HMG-box and C1 domains in complex with an 18-base-pair DNA oligomer containing a consensus octameric CIC binding site. We find that both protein domains adopt independent tri-helical structures that pack against opposite sides of the DNA helix. The C1 domain in particular folds into a helix-turn-helix (HTH) structure that resembles the FF phosphoprotein binding domain. It inserts into the major groove of the DNA and plays a direct role in enhancing both the affinity and sequence specificity of CIC DNA binding. Our results reveal a unique bipartite protein module, ensuring highly specific DNA recognition by CIC, and show how this mechanism is disrupted by cancer mutations affecting either the HMG-box or C1 domains.

HMG-box

B3 domain

10.1101/2022.03.28.485992

Cite

Citations (4)

Substrate specificity of the sulfur assimilation enzyme SfnG

Ngan Thi Ngoc Phan Jeremy Liew Daniel P. Dowling Denyce K. Wicht

Assimilation (phonology)

10.1021/scimeetings.0c01995

Cite

Citations (0)

Substrate specificity of the sulfur assimilation enzyme SfnG