The second AT-hook of HMGA1 (black ribbon) bound to the minor-groove of AT-rich DNA. The amino-acid side chains and nucleotides have been hidden. The AT-hook is a DNA-binding motif present in many proteins, including the high mobility group (HMG)

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s, DNA-binding

s from

plants Plants are the eukaryotes that form the kingdom Plantae; they are predominantly photosynthetic. This means that they obtain their energy from sunlight, using chloroplasts derived from endosymbiosis with cyanobacteria to produce sugars f ...

and hBRG1 protein, a central ATPase of the

human Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...

switching/sucrose non-fermenting (SWI/SNF) remodeling

complex Complex commonly refers to: * Complexity, the behaviour of a system whose components interact in multiple ways so possible interactions are difficult to describe ** Complex system, a system composed of many components which may interact with each ...

Structure

This motif consists of a conserved, palindromic, core sequence of proline-

arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (G ...

- proline, although some AT-hooks contain only a single proline in the core sequence. AT-hooks also include a variable number of positively charged

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...

and

residues on either side of the core sequence. The AT-hook binds to the minor groove of

adenine Adenine (, ) (nucleoside#List of nucleosides and corresponding nucleobases, symbol A or Ade) is a purine nucleotide base that is found in DNA, RNA, and Adenosine triphosphate, ATP. Usually a white crystalline subtance. The shape of adenine is ...

thymine Thymine () (symbol T or Thy) is one of the four nucleotide bases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine ...

(AT) rich DNA, hence the AT in the name. The rest of the name derives from a predicted asparagine/ aspartate "hook" in the earliest AT-hooks reported in 1990. In 1997 structural studies using

NMR Nuclear magnetic resonance (NMR) is a physical phenomenon in which atomic nucleus, nuclei in a strong constant magnetic field are disturbed by a weak oscillating magnetic field (in the near and far field, near field) and respond by producing ...

determined that a DNA-bound AT-hook adopted a crescent or hook shape around the minor groove of a target DNA strand (pictured at right). HMGA proteins contain three AT-hooks, although some proteins contain as many as 30. The optimal binding sequences for AT-hook proteins are repeats of the form (ATAA)_n or (TATT)_n, although the optimal binding sequences for the core sequence of the AT-hook are AAAT and AATT. The DNA dodecamer has eight consecutive AT base pairs, allowing the AT-hook to be positioned in several positions, with the preferred position being at one of the AATT regions to fully occupy the minor groove. Van der Waals interactions of the AT-hook with the adenines play an important role for the specificity of the position. Van der Waals interactions of the AT-hook with the adenines play an important role for the specificity of the position. AT-Hook PyMol 1

The figure shows the position of the main chain to allow hydrogen bonds with the minor groove thymine oxygen atoms. The interactions shown, caused the DNA to bend, extending the minor groove. The distorted DNA causes the complementary major groove to form interactions between the side chains.

Function

AT-hook proteins can form hydrogen bonds between NH groups of Gly37 and Arg38 on the main-chain and thymine oxygen atoms in the minor groove, which bends the DNA and widens the minor groove. The binding to the minor groove facilitates binding of other proteins in the major groove. That enables HMG proteins to regular expression of genes and influence biological processes. The AT-hooks have also been proposed to anchor chromatin-modifying proteins to AT-rich DNA sequences through their association with chromatin remodeling, histone modifications, and chromatin insulator function.

Clinical significance

Alterations or abnormal expression of the HMG proteins have led to metabolic disorders, such as obesity, type 2 diabetes, and cancer.

References

{{reflist Genetics techniques Molecular genetics