Biomedical subjects

Mark D Allen

Publications and source records attributed to Mark D Allen.

23 records · Page 2Linked to original sources

PubMed2003

Structure of the Jab1/MPN domain and its implications for proteasome function.

The 26S proteasome is responsible for the degradation of polyubiquitinated proteins. During this process the polyubiquitin chain is removed. The identity of the proteasomal component that is responsible for this activity has not been clear, as it contains no subunits that resemble known deubiquitinating enzymes. The Jab1/MPN domain is a widespread 120 amino acid protein module found in archaea, bacteria, and eukaryotes. In eukaryotes the Jab1/MPN domain is found in subunits of several multiprotein complexes including the proteasome. Recently it has been proposed that the Jab1/MPN domain of the proteasomal subunit Rpn11 is responsible for the removal of the polyubiquitin chain from substrate proteins. Here we report the crystal structure and characterization of AF2198, a Jab1/MPN domain protein from Archaeoglobolus fulgidus. The structure reveals a fold that resembles that of cytidine deaminase and places the Jab1/MPN domain in a superfamily of metal dependent hydrolases.

Amino Acid Motifs↗

PubMed2003

Crystal structure of the malignant brain tumor (MBT) repeats in Sex Comb on Midleg-like 2 (SCML2).

Sex Comb on Midleg (SCM) belongs to the Polycomb group of proteins, which are involved in transcriptional regulation in Drosophila. It is one of the components of Polycomb repressive complex 1, a multiprotein complex of Polycomb group proteins involved in the maintenance of repression and the blocking of chromatin remodeling. SCM contains two approximately 100-residue malignant brain tumor (MBT) repeats at the N terminus. These repeats are also found in other proteins involved in transcriptional repression. Here, we report the 1.78-A crystal structure of the two MBT repeats of SCM-like 2 (SCML2), a human homologue of SCM. Each repeat consists of an extended arm and a beta-barrel core. There are significant structural similarities to the Tudor, PWWP, and chromo domains, suggesting probable evolutionary relationships and functional similarities between the MBT repeats and these domains.

Amino Acid Sequence↗

PubMed2003

Structural variation in PWWP domains.

The PWWP domain is a ubiquitous eukaryotic protein module characterised by a region of sequence similarity of approximately 80 amino acids containing a highly conserved PWWP motif. It is frequently found in proteins associated with chromatin. We have determined the structure of a PWWP domain from the S. pombe protein SPBC215.07c using NMR spectroscopy. The structure is composed of a five stranded beta barrel followed by two alpha helices. Comparison to the recently reported structure of a homologous domain from the mammalian DNA methyltransferase Dnmt3b reveals substantial differences both in the C-terminal helical region and in the PWWP motif.

Amino Acid Sequence↗

PubMed2003

The crystal structure of AF1521 a protein from Archaeoglobus fulgidus with homology to the non-histone domain of macroH2A.

MacroH2A is an unusual histone H2A variant that has an extensive C-terminal tail that comprises approximately two thirds of the protein. The C-terminal non-histone domain of macroH2A is also found in a number of other proteins and has been termed the macro domain. Here we report the crystal structure to 1.7A of AF1521, a protein consisting of a stand-alone macro domain from Archaeoglobus fulgidus. The structure has a mixed alpha/beta fold that closely resembles the N-terminal DNA binding domain of the Escherichia coli leucine aminopeptidase PepA. The structure also shows some similarity to members of the P-loop family of nucleotide hydrolases.

Amino Acid Sequence↗

PubMed2002

Brain potentials elicited by prose-embedded linguistic anomalies.

Linguistic theories distinguish between syntax (sentence form) and semantics (sentence meaning). Correspondingly, recent studies have shown that syntactic and semantic anomalies elicit distinct changes in the event-related brain potential (ERP). However, these results have been obtained with highly artificial methodologies and have not yet been generalized to more natural reading conditions. Here, we recorded ERPs while subjects read a naturalistic prose passage. The subjects either read for comprehension with no other task being assigned or read for comprehension and made acceptability judgments after each sentence. Consistent with prior work and regardless of the subjects' assigned task, syntactic anomalies elicited a large positive wave (P600), whereas semantic anomalies elicited a large increase in N400 amplitude. These results demonstrate that the qualitatively distinct ERP responses elicited by syntactic and semantic anomalies are not artifacts of unnatural aspects of previously used stimuli, thereby providing additional evidence that separable syntactic and semantic processes exist.

Adolescent↗