In Silico Modeling and Docking of SPECC1L Coiled Coil Domain with hMps1 Tetratricopeptide Repeat

Authors: Mattison, Chris

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 9/7/2021
Publication Date: N/A
Citation: N/A

Interpretive Summary: Interactions between proteins are responsible for almost every aspect of life. Interactions between signaling and structural proteins within a cell govern growth, cell division, and response to stress. Signaling proteins allow us to adapt to changes in our environment and structural proteins ensure the shape and integrity of our cells. The Sperm Antigen with Calponin Homology and Coiled-Coil Domains 1 Like (SPECC1L) protein is involved in several aspects of cell biology and is expressed in intestinal tissues. The SPECC1L protein is thought to be involved in cellular functions essential for proper gut function and cellular communication. The SPECC1L protein associates with both structural and signaling proteins. One important signaling protein that SPECC1L is thought to interact with is the human Mono-Polar Spindles (hMps1) protein kinase. The hMps1 protein is involved in several essential cellular functions and is likely important for sub-cellular structures that ensure proper immune system sampling of allergens within the gut. The SPECC1L protein contains segments that have been previously shown to interact with part of the hMps1 protein. A crystal structure for the hMps1 protein has been solved, and computer modeling was used to predict SPECC1L protein structure and predict how hMps1 might associate with SPECC1L. The modeling results suggest SPECC1L forms long coiled segments, and docking results between the two proteins indicate a groove within the hMps1 protein interacts with SPECC1L. The modeling results presented here may help us understand what specific role the interaction between SPECC1L and hMps1 plays in cell biology.

Technical Abstract: The Sperm Antigen with Calponin Homology and Coiled-Coil Domains 1 Like (SPECC1L) protein is involved in several aspects of cell biology and is expressed in many tissues, including intestinal cells. The SPECC1L protein is thought to be involved in cellular functions essential for proper gut function and cellular communication. The SPECC1L protein associates with both tubulin and actin filaments, and loss of SPECC1L results in cytokinesis, cell adhesion, gap junction defects, and oblique facial clefting. The human Mono-Polar Spindles (hMps1) protein kinase is involved in the spindle assembly checkpoint and cytokinesis, and defects in hMps1 affect checkpoint signaling and are associated with some types of cancer. Proper hMps1 function is likely important for sub-cellular structures that ensure proper immune system sampling of allergens within the gut. The SPECC1L protein contains calponin homology (CH) and coiled coil (CC) domains, and a segment of the protein (amino acids 45-659) was previously isolated in a yeast 2-hybrid screen with the amino terminus (amino acids 1-311) of hMps1. The consequence of the interaction between SPECC1L and hMps1 is not understood. Amino acids 1-311 of hMps1 contain a tetratricopeptide repeat (TPR) and a crystal structure for the hMps1 TPR has been solved. In silico modeling was used to predict SPECC1L CC domain structure and dock the structure to the hMps1 TPR. Modeling suggests the SPECC1L CC domain forms paired alpha helical coils, and docking results indicate a groove within the hMps1 TPR interacts with specific residues within the SPECC1L CC domain. SPECC1L functions to interact with and stabilize the cellular structural framework including the actin and microtubule networks. The results of the in silico modeling presented here may enable improved understanding of the interaction between these two proteins and the role it plays in cell biology.