User:Brian Boyle/Sandbox 1: Difference between revisions
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'''Peregrin''', also known as Bromodomain and PHD Finger-containing 1 ('''BRPF1''') is a 137 kDa protein that plays a versatile role in epigenetic signaling events. It contains three chromatin reader domains, including a <scene name='91/910741/Apo_bromodomain/1'>bromodomain</scene>, <scene name='91/910741/Apo_pzp/1'>PZP domain</scene> (two PDH fingers separated by a Zinc Knuckle), and '''proline-tryptophan-tryptophan-proline (<scene name='91/910741/Pwwp_unliganded/1'>PWWP</scene>) domain''' <ref name="Yan">PMID:27939640</ref>. Through these three domains, it is capable of recognizing both modified and unmodified histones, as well as non-specifically binding DNA <ref>PMID:31711755</ref>,<ref name="Glass1">PMID:24333487</ref>. BRPF1 carries out its function as a component of the MOZ (monocytic leukemic zinc-finger protein) histone acetyltransferase (HAT) complex <ref name="Obi">PMID:33554132</ref>. This complex is involved in the regulation of gene expression, particularly those involved with skeletal development and hematopoiesis <ref>PMID:19254709</ref>,<ref>PMID:27500495</ref>. | '''Peregrin''', also known as Bromodomain and PHD Finger-containing 1 ('''BRPF1''') is a 137 kDa protein that plays a versatile role in epigenetic signaling events. It contains three chromatin reader domains, including a <scene name='91/910741/Apo_bromodomain/1'>bromodomain</scene>, <scene name='91/910741/Apo_pzp/1'>PZP domain</scene> (two PDH fingers separated by a Zinc Knuckle), and '''proline-tryptophan-tryptophan-proline (<scene name='91/910741/Pwwp_unliganded/1'>PWWP</scene>) domain''' <ref name="Yan">PMID:27939640</ref>. Through these three domains, it is capable of recognizing both modified and unmodified histones, as well as non-specifically binding DNA <ref>PMID:31711755</ref>,<ref name="Glass1">PMID:24333487</ref>. BRPF1 carries out its function as a component of the MOZ (monocytic leukemic zinc-finger protein) histone acetyltransferase (HAT) complex <ref name="Obi">PMID:33554132</ref>. This complex is involved in the regulation of gene expression, particularly those involved with skeletal development and hematopoiesis <ref>PMID:19254709</ref>,<ref>PMID:27500495</ref>. | ||
== '''PZP Domain''' == | |||
== '''Bromodomain Structure & Acetyllysine Recognition''' == | == '''Bromodomain Structure & Acetyllysine Recognition''' == | ||
Consistent with most bromodomains, the BRPF1 bromodomain consists of a four α-helical bundle. These helices are termed <scene name='91/910741/Helical_bundle/3'>αZ, αA, αB, and αC</scene> (from N to C terminus)<ref name="Lubula_2014">PMID:25281266</ref>. | Consistent with most bromodomains, the BRPF1 bromodomain consists of a four α-helical bundle. These helices are termed <scene name='91/910741/Helical_bundle/3'>αZ, αA, αB, and αC</scene> (from N to C terminus)<ref name="Lubula_2014">PMID:25281266</ref>. | ||
The BRPF1 bromodomain has been shown to recognize and bind to various acetylated lysine marks on the N-terminal tails of histones tails <ref name="Glass1" />. Using isothermal titration calorimetry (ITC) experiments, it was found that the BRPF1 bromodomain preferentially binds to histone H4 acetylated at positions K5 ([[2rs9]]) and K12 ([[4qyd]]) as well as H2A at position K5 ([[4qyl]]) <ref name="Obi" />,<ref>PMID:24333487</ref>. Interestingly, the BRPF1 bromodomain has also been shown to bind di-acetylated histone peptides with high affinity, including H4K5acK8ac and H4K5acK12ac <ref name="Obi" />. Acetyllysine recognition is coordinated by a number of residues in the bromodomain's binding pocket. Using NMR chemical shift perturbation experiments, Glass et al. reported several <scene name='91/910741/Nmr_resi_h4_binding/1'>key residues</scene> involved in coordinating histone H4 ligands (I27, L34, E36, V37, N83, and I88)<ref name="Obi" />. Notably, asparagine 83 was among these. The interactions between the amide nitrogen of asparagine with the carbonyl of the acetyllysine group is conserved in all bromodomains and is necessary for binding to occur <ref name ="Obi" />,<ref name ="Lubula_2014" />. | The BRPF1 bromodomain has been shown to recognize and bind to various acetylated lysine marks on the N-terminal tails of histones tails <ref name="Glass1" />. Using isothermal titration calorimetry (ITC) experiments, it was found that the BRPF1 bromodomain preferentially binds to histone H4 acetylated at positions K5 ([[2rs9]]) and K12 ([[4qyd]]) as well as H2A at position K5 ([[4qyl]]) <ref name="Obi" />,<ref>PMID:24333487</ref>. Interestingly, the BRPF1 bromodomain has also been shown to bind di-acetylated histone peptides with high affinity, including H4K5acK8ac and H4K5acK12ac <ref name="Obi" />. Acetyllysine recognition is coordinated by a number of residues in the bromodomain's binding pocket. Using NMR chemical shift perturbation experiments, Glass et al. reported several <scene name='91/910741/Nmr_resi_h4_binding/1'>key residues</scene> involved in coordinating histone H4 ligands (I27, L34, E36, V37, N83, and I88)<ref name="Obi" />. Notably, asparagine 83 was among these. The interactions between the amide nitrogen of asparagine with the carbonyl of the acetyllysine group is conserved in all bromodomains and is necessary for binding to occur <ref name ="Obi" />,<ref name ="Lubula_2014" />. | ||
== '''PWWP Domain''' == | |||
== '''Role in Disease Progression''' == | == '''Role in Disease Progression''' == | ||
Revision as of 04:33, 2 May 2022
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