Domain swapping and SMYD1 interactions with the PWWP domain of human hepatoma-derived growth factor.

Abstract:

:The human hepatoma-derived growth factor (HDGF), containing the chromatin-associated N-terminal PWWP domain capable of binding the SMYD1 promoter, participates in various cellular processes and is involved in human cancers. We report the first crystal structures of the human HDGF PWWP domain (residues 1-100) in a complex with SMYD1 of 10 bp at 2.84 Å resolution and its apo form at 3.3 Å, respectively. The structure of the apo PWWP domain comprises mainly four β-strands and two α-helices. The PWWP domain undergoes domain swapping to dramatically transform its secondary structures, altering the overall conformation from monomeric globular folding into an extended dimeric structure upon DNA binding. The flexible loop2, as a hinge loop with the partially built structure in the apo PWWP domain, notably refolds into a visible and stable α-helix in the DNA complex. The swapped PWWP domain interacts with the minor grooves of the DNA through residues Lys19, Gly22, Arg79 and Lys80 in varied ways on loops 1 and 4 of the two chains, and the structure becomes more rigid than the apo form. These novel structural findings, together with physiological and activity assays of HDGF and the PWWP domain, provide new insights into the DNA-binding mechanism of HDGF during nucleosomal functions.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Chen LY,Huang YC,Huang ST,Hsieh YC,Guan HH,Chen NC,Chuankhayan P,Yoshimura M,Tai MH,Chen CJ

doi

10.1038/s41598-017-18510-8

subject

Has Abstract

pub_date

2018-01-10 00:00:00

pages

287

issue

1

issn

2045-2322

pii

10.1038/s41598-017-18510-8

journal_volume

8

pub_type

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