HMG-box

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HMG (high mobility group) box
2LEF.png
NMR structure of the HMG-box domain of the LEF1 protein (rainbow colored, N-terminus = blue, C-terminus = red) complexed with DNA (brown) based on the PDB: 2LEF coordinates.
Identifiers
SymbolPF00505
Pfam PF00505
InterPro IPR009071
SCOP2 1hsm / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
PDB 1aab , 1cg7 , 1ckt , 1e7j , 1gt0 , 1hme , 1hmf , 1hry , 1hrz , 1hsm , 1hsn , 1i11 , 1j3x , 1j46 , 1j47 , 1j5n , 1k99 , 1lwm , 1nhm , 1nhn , 1o4x , 1qrv , 1s9m , 1sx9 , 1v64 , 1wgf , 1wxl , 2crj , 2cs1 , 2lef

In molecular biology, the HMG-box (high mobility group box) is a protein domain which is involved in DNA binding. [1] The domain is composed of approximately 75 amino acid residues that collectively mediate the DNA-binding of chromatin-associated high-mobility group proteins. HMG-boxes are present in many transcription factors and chromatin-remodeling complexes, where they can mediate non-sequence or sequence-specific DNA binding. [2]

Contents

Structure

The structure of the HMG-box domain contains three alpha helices separated by loops (see figure to the right). [3]

Function

HMG-box containing proteins only bind non-B-type DNA conformations (kinked or unwound) with high affinity. [1] HMG-box domains are found in some high mobility group proteins, which are involved in the regulation of DNA-dependent processes such as transcription, replication, and DNA repair, all of which require changing the conformation of chromatin. [3] The single and the double box HMG proteins alter DNA architecture by inducing bends upon binding. [4] [5]

Related Research Articles

Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in reinforcing the DNA during cell division, preventing DNA damage, and regulating gene expression and DNA replication. During mitosis and meiosis, chromatin facilitates proper segregation of the chromosomes in anaphase; the characteristic shapes of chromosomes visible during this stage are the result of DNA being coiled into highly condensed chromatin.

<span class="mw-page-title-main">Transcription factor</span> Protein that regulates the rate of DNA transcription

In molecular biology, a transcription factor (TF) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The function of TFs is to regulate—turn on and off—genes in order to make sure that they are expressed in the desired cells at the right time and in the right amount throughout the life of the cell and the organism. Groups of TFs function in a coordinated fashion to direct cell division, cell growth, and cell death throughout life; cell migration and organization during embryonic development; and intermittently in response to signals from outside the cell, such as a hormone. There are approximately 1600 TFs in the human genome. Transcription factors are members of the proteome as well as regulome.

<span class="mw-page-title-main">DNA-binding protein</span> Proteins that bind with DNA, such as transcription factors, polymerases, nucleases and histones

DNA-binding proteins are proteins that have DNA-binding domains and thus have a specific or general affinity for single- or double-stranded DNA. Sequence-specific DNA-binding proteins generally interact with the major groove of B-DNA, because it exposes more functional groups that identify a base pair.

HMGN proteins are members of the broader class of high mobility group (HMG) chromosomal proteins that are involved in regulation of transcription, replication, recombination, and DNA repair.

A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one structural motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence or have a general affinity to DNA. Some DNA-binding domains may also include nucleic acids in their folded structure.

SOX genes encode a family of transcription factors that bind to the minor groove in DNA, and belong to a super-family of genes characterized by a homologous sequence called the HMG-box. This HMG box is a DNA binding domain that is highly conserved throughout eukaryotic species. Homologues have been identified in insects, nematodes, amphibians, reptiles, birds and a range of mammals. However, HMG boxes can be very diverse in nature, with only a few amino acids being conserved between species.

High-Mobility Group or HMG is a group of chromosomal proteins that are involved in the regulation of DNA-dependent processes such as transcription, replication, recombination, and DNA repair.

<span class="mw-page-title-main">CTCF</span> Transcription factor

Transcriptional repressor CTCF also known as 11-zinc finger protein or CCCTC-binding factor is a transcription factor that in humans is encoded by the CTCF gene. CTCF is involved in many cellular processes, including transcriptional regulation, insulator activity, V(D)J recombination and regulation of chromatin architecture.

Dame Jean Olwen Thomas, is a Welsh biochemist, former Master of St Catharine's College, Cambridge, and Chancellor of Swansea University.

<span class="mw-page-title-main">HMGA2</span> Protein-coding gene in the species Homo sapiens

High-mobility group AT-hook 2, also known as HMGA2, is a protein that, in humans, is encoded by the HMGA2 gene.

<span class="mw-page-title-main">HMGB1</span> Mammalian protein found in Homo sapiens

High mobility group box 1 protein, also known as high-mobility group protein 1 (HMG-1) and amphoterin, is a protein that in humans is encoded by the HMGB1 gene.

<span class="mw-page-title-main">HMGA1</span> Protein-coding gene in the species Homo sapiens

High-mobility group protein HMG-I/HMG-Y is a protein that in humans is encoded by the HMGA1 gene.

<span class="mw-page-title-main">Structure specific recognition protein 1</span> Protein-coding gene in the species Homo sapiens

FACT complex subunit SSRP1 also known as structure specific recognition protein 1 is a protein that in humans is encoded by the SSRP1 gene.

<span class="mw-page-title-main">HMGB2</span> Protein-coding gene in the species Homo sapiens

High-mobility group protein B2 also known as high-mobility group protein 2 (HMG-2) is a protein that in humans is encoded by the HMGB2 gene.

<span class="mw-page-title-main">HMGN1</span> Protein-coding gene in the species Homo sapiens

Non-histone chromosomal protein HMG-14 is a protein that in humans is encoded by the HMGN1 gene.

<span class="mw-page-title-main">SOX12</span> Protein-coding gene in the species Homo sapiens

SOX12 is a protein that in humans is encoded by the SOX12 gene. Sox12 belongs to the SoxC group of Sox family of transcription factors, together with Sox4 and Sox11. Sox12-null knockout mice appear normal, unlike Sox4 or Sox11 knockout mice. This probably comes from functional redundancy with Sox4 and Sox11. Sox12 is a weaker activator than both Sox4 and Sox11 in mouse.

TOX high mobility group box family member 2, also known as TOX2, is a human gene.

TOX high mobility group box family member 3, also known as TOX3, is a human gene.

<span class="mw-page-title-main">AT-hook</span>

The AT-hook is a DNA-binding motif present in many proteins, including the high mobility group (HMG) proteins, DNA-binding proteins from plants and hBRG1 protein, a central ATPase of the human switching/sucrose non-fermenting (SWI/SNF) remodeling complex.

High mobility group protein HMG14 and HMG17 also known as nucleosomal binding domain is a family of evolutionarily related proteins.

References

  1. 1 2 Stros M, Launholt D, Grasser KD (October 2007). "The HMG-box: a versatile protein domain occurring in a wide variety of DNA-binding proteins". Cell. Mol. Life Sci. 64 (19–20): 2590–606. doi:10.1007/s00018-007-7162-3. PMID   17599239. S2CID   28156847.
  2. Štros, M.; Launholt, D.; Grasser, K. D. (October 2007). "The HMG-box: a versatile protein domain occurring in a wide variety of DNA-binding proteins". Cellular and Molecular Life Sciences. 64 (19–20): 2590–2606. doi:10.1007/s00018-007-7162-3. PMID   17599239 . Retrieved 18 February 2023.
  3. 1 2 Thomas JO (August 2001). "HMG1 and 2: architectural DNA-binding proteins". Biochem. Soc. Trans. 29 (Pt 4): 395–401. doi:10.1042/BST0290395. PMID   11497996.
  4. D. Murugesapillai et al, DNA bridging and looping by HMO1 provides a mechanism for stabilizing nucleosome-free chromatin, Nucleic Acids Res (2014) 42 (14): 8996-9004
  5. D. Murugesapillai et al, Single-molecule studies of high-mobility group B architectural DNA bending proteins, Biophys Rev (2016) doi:10.1007/s12551-016-0236-4